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1
Sundman, Mark H., Nan-kuei Chen, Vignesh Subbian et Ying-hui Chou. « The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease ». ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017. http://hdl.handle.net/10150/626124.
Texte intégralRésumé :
As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
2
Rincel, Marion. « Role of the gut-brain axis in early stress-induced emotional vulnerability ». Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0870/document.
Texte intégralRésumé :
Les maladies psychiatriques présentent de fortes comorbidités avec des désordres gastrointestinaux, ce qui suggère l’existence de bases physiopathologiques communes. Une littérature abondante démontre que l’adversité précoce (infection, stress) augmente la vulnérabilité aux désordres psychiatriques à l’âge adulte. Chez le rongeur, le modèle de séparation maternelle induit chez la descendance adulte des comportements hyperanxieux associés à une hypersensibilité au stress, ainsi que des dysfonctionnements de la sphère gastrointestinale. De plus, des études récentes rapportent une hyperperméabilité de la barrière intestinale chez les ratons soumis au stress de séparation, un effet conduisant potentiellement à une dysbiose et une perturbation de la communication intestin-cerveau. Le but de ma thèse était donc d’étudier le rôle de l’axe intestin-cerveau dans la mise en place des effets à long terme du stress précoce. Nos travaux récents ont montré que certains effets à long-terme de la séparation maternelle peuvent être atténués par l’exposition des mères à un régime hyperlipidique. Dans un premier temps, nous avons testé les effets du régime hyperlipidique maternel sur le cerveau et l’intestin de ratons soumis à la séparation maternelle. Nos résultats montrent que le régime maternel hyperlipidique protège de l’augmentation de la permeabilité intestinale induite par le stress. Nous avons ensuite testé le rôle causal de la perméabilité intestinale sur les comportements émotionnels à travers une approche pharmacologique et une approche génétique. Nous rapportons 1) que la restauration de la fonction barrière de l’intestin atténue certains effets de la séparation maternelle et 2) qu’une hyperperméabilité intestinale chez des souris transgéniques non soumises à un stress produit des effets similaires à ceux de la séparation maternelle. Enfin, nous avons examiné les effets d’une adversité précoce multifactorielle sur le cerveau et l’intestin (perméabilité et microbiote) chez la descendance adulte mâle et femelle dans un modèle combinant infection prénatale et séparation maternelle. Nos résultats mettent en évidence un effet sexe très marqué sur les phénotypes comportements et intestinaux. D’autres études sont nécessaires pour identifier les mécanismes sous-tendant les effets de la perméabilité et la dysbiose intestinale sur la vulnérabilité émotionnelle associée au stress précoceEarly-life adversity is a main risk factor for psychiatric disorders at adulthood; however the mechanisms underlying the programming effect of stress during development are still unknown. In rodents, chronic maternal separation has long lasting effects in adult offspring, including hyper-anxiety and hyper-responsiveness to a novel stress, along with gastrointestinal dysfunctions. Moreover, recent studies report gut barrier hyper-permeability in rat pups submitted to maternal separation, an effect that could potentially lead to dysbiosis and altered gut-brain communication. Therefore, the aim of my PhD was to unravel the role of the gut-brain axis in the neurobehavioral effects of early-life stress. We recently reported that some neural, behavioral and endocrine alterations associated with maternal separation in rats could be prevented by maternal exposure to a high-fat diet. We first addressed the effects of maternal high-fat diet on brain and gut during development in the maternal separation model. We show that maternal high-fat diet prevents the stress-induced decrease in spine density and altered dendritic morphology in the medial prefrontal cortex. Moreover, maternal high-fat diet also attenuates the exacerbated intestinal permeability associated with maternal separation. To explore a potential causal impact of gut leakiness on brain functions, we then examined the impact of pharmacological and genetic manipulations of intestinal permeability on brain and behavior. We report 1) that restoration of gut barrier function attenuates some of the behavioral alterations associated with maternal separation and 2) that chronic gut leakiness in naive adult transgenic mice recapitulates the effects of maternal separation. Finally, we examined the effects of multifactorial early-life adversity on behavior, gut function and microbiota composition in males and females using a combination of prenatal inflammation and maternal separation in mice. At adulthood, offspring exposed to early adversity displayed sex-specific behavioral (social behavior deficits in males and increased anxiety in females) and intestinal phenotypes. In conclusion, our work demonstrates an impact of gut dysfunctions, in particular gut leakiness, on the emergence of emotional alterations. Further studies are needed to unravel the role of the gut dysbiosis in the expression of the behavioral phenotypes associated with early-life adversity
3
Marsilio, Ilaria. « Functional and Molecular Studies of the Crosstalk between Intestinal Microbioma and Enteric Nervous System and Potential Effects on the Gut-Brain Axis ». Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3427312.
Texte intégralRésumé :
L'interazione fra costituenti della parete intestinale e microflora commensale costituisce il principale artefice del mantenimento della barriera mucosale, della promozione dello sviluppo del tratto gastrointestinale (GI) e della modulazione delle funzioni GI. In questo contesto, giocano un ruolo chiave i recettori Toll-like (TLRs), un sistema di proteine che attivano la risposta immunitaria innata e assicurano l'integrità funzionale e strutturale del SNE. In questo studio sono state caratterizzate le alterazioni strutturali e funzionali del SNE murino indotte da: i) cambiamenti nel segnale dell’immunità innata, mediato dal recettore TLR4, ii) una miscela di fosfolipidi ossidati (OxPAPC), implicati nel blocco del segnale generato dai recettori TLR2 e TLR4 e iii) anomalie nella composizione del microbiota.
Data l’importanza di un corretto segnale TLRs-dipendente nel mantenimento della rete nervosa e del codice neurochimico del SNE, segmenti di ileo provenienti da topi WT e TLR4-/- hanno evidenziato anomalie nell’attività contrattile neuromuscolare associate ad un’eccessiva modulazione inibitoria da NO ed ATP, a sostegno della presenza di un dialogo tra TLR4, SNE e microflora, fondamentale per la modulazione della funzione neuromuscolare. Studi strutturali su preparati di ileo di topi TLR4-/- evidenziano un’alterata architettura del SNE a livello gliale, indicando un coinvolgimento del recettore TLR4 nel mantenimento dell'integrità della rete gliale enterica mediato dalla produzione di ATP e della trasmissione purinergica evidenziano il ruolo di TLR4 nell’omeostasi strutturale e funzionale del SNE. Inoltre, è stato dimostrato che la mancanza del recettore TLR4 determina nell’ippocampo, come a livello del SNE, una compromessa neuroplasticità caratterizzata da alterazioni nella densità neuronale associata a variazioni della distribuzione della rete gliale, a confermare un ruolo fondamentale del segnale TLRs anche a livello centrale.
In parallelo, è stato indagato il ruolo del segnale mediato dai TLRs nell’asse microbiota-TLRs-SNE, tramite la somministrazione in acuto con OxPAPC, inibitore del segnale mediato da entrambi i recettori TLR2 e TLR4, in topi adolescenti (3 ± 1 settimane). Il trattamento con OxPAPC ha causato un’alterazione significativa della risposta neuromuscolare associata a modifiche della rete neuro-gliale del SNE, confermando l’importanza del segnale mediato da tali recettori nell'assicurare l’integrità funzionale e strutturale del SNE durante l'adolescenza. Recenti studi riportano un ruolo primario nel dialogo tra i recettori TLRs e il sistema serotoninergico ed è stato evidenziato come OxPAPC comporti iperesponsività alla serotonina, alterazioni nella distribuzione recettoriale serotoninergica associata a variazioni nel metabolismo del triptofano, a sostegno della presenza di un dialogo tra immunità innata e sistema serotoninergico.
Al fine di approfondire il ruolo dell'asse microbiota-intestino nell’omeostasi del SNE è stato messo a punto un modello animale di deplezione di microbiota intestinale attraverso la somministrazione di 4 antibiotici a topi adolescenti. Tale trattamento ha determinato un fenotipo simil germ-free ed alterazioni della motilità intestinale e dell'integrità della rete neuronale e gliale enterica. Data l’importanza di una corretta composizione del microbiota commensale nel mantenimento del codice neurochimico del SNE che nella produzione di neurotrasmettitori a livello enterico, sono state studiate le vie di neurotrasmissione coinvolte nella sensibilità viscerale. Un’alterata composizione del microbiota intestinale altera la sensibilità viscerale associata anomalie nella risposta neuromuscolare alla serotonina accompagnate da una compromessa rete recettoriale serotoninergica e del metabolismo del triptofano, sottolineando l’importanza di una corretta composizione del microbiota nel mantenimento delle funzioni mediate dal sistema serotoninergico.
4
Charton, Elise. « Lait humain vs. préparation pour nourrissons : digestibilité des protéines et impact sur l’axe microbiote-intestin-cerveau ». Electronic Thesis or Diss., Rennes, Agrocampus Ouest, 2023. http://www.theses.fr/2023NSARB368.
Texte intégralRésumé :
Une majorité de nourrissons reçoivent encore aujourd’hui des préparations pour nourrissons (PPN), fabriquées à base de lait bovin et soumises à de nombreux traitements technologiques. Ces substituts ont pour but de mimer au mieux le lait humain (LH). Cependant, malgré l’évolution des PPNs, des différences persistent entre le LH et les PPNs en termes de composition et structure, et effets sur le développement et la santé à court et long termes du nourrisson et adulte en devenir. L’objectif de ce travail était de comprendre comment la nature de l’alimentation infantile, LH vs. PPN, modulait la digestibilité protéique et, plus globalement, comment elle influençait l’axe microbiote intestin-cerveau. Deux modèles du nourrisson humain ont été utilisés et comparés, le mini-porc Yucatan entre 16 et 21 jours de vie, et un modèle de digestion in vitro dynamique paramétré pour mimer le nourrisson à terme. Les contenus digestifs et tissus ont ensuite été analysés via des approches métagénomique (microbiote), histologique et de perméabilité ex vivo (physiologie intestinale), d’expression génique et de métabolomique ciblée (intestin, cerveau et plasma). Les résultats ont montré que la digestibilité de l’azote total et dans une moindre mesure, celle de certains acides aminés (Lys, Phe, Thr, Val, Ala, Pro et Ser) différaient entre LH et PPN. Les deux modèles de digestion (in vivo et in vitro) étudiés ont conduit à des résultats similaires en termes de déstructuration des aliments et du taux de protéines intactes résiduelles en phase gastrique. Le modèle de digestion in vitro dynamique utilisé ici est donc un bon outil de prédiction de la digestion in vivo. L’axe microbiote-intestin-cerveau et notamment la composition du microbiote, ainsi que le métabolisme du tryptophane, malgré une digestibilité similaire entre aliments, étaient modulés différemment par le LH et la PPN. L’augmentation de la permeabilité intestinale, bien que modérée, était associée à un renforcement du système immunitaire mucosal avec le LH. Ces modifications sont associées à des changements d’expression génique (fonctions barrière et endocrine, récepteurs aux AGV) aux niveaux hypothalamique et striatal, et de profils métaboliques principalement aux niveaux hippocampique et plasmatique. Certains composants présents dans le LH (ex.: oligosaccharides, azote non protéique tel que l’urée, consortium bactérien) et absent dans la PPN peuvent expliquer ces résultats. La supplémentation des PPNs en ces composants bioactifs et/ou la modulation de la fraction protéique pourraient être des leviers pour l’optimisation des PPNsNowadays, a high rate of infants is still being fed infant formulas (IF) based on cow milk and subjected to several technological treatments. These substitutes aim to mimic as close as possible the human milk (HM). Despite of IF improvement, differences still exist between HM and IF in terms of composition and structure, and effects on health in infancy, and later on in adulthood. The objective of this work was to understand how the infant food modulated the dietary nitrogen digestibility and, in overall, how it shaped the microbiota-gut-brain axis. Two infant models were used and compared, the 16 to 21-day-old mini-piglet Yucatan and an in vitro dynamic digestion model parametered with term infant digestive conditions. Digestive contents and tissues were then analyzed using metagenomic (microbiota), histological and ex vivo permeability (intestinal physiology) approaches, gene expression and targeted-metabolomic approaches (intestine, brain and plasma). The results showed that the digestibility of nitrogen and at least extent, that of a few amino acids (Lys, Phe, Thr, Val, Ala, Pro and Ser) were different between HM and IF. The two digestion models (in vivo and in vitro) led to similar observations in terms of meal deconstruction and proteolysis, showing that the in vitro dynamic digestion model is a good proxy of the in vivo digestion regarding digestion kinetics. The microbiota-gut-brain axis, notably regarding the colonic microbial composition and the tryptophan metabolism, which digestibility was similar between infant foods, were differently modulated by HM and IF. The increase of the intestinal permeability, though moderately, was associated with a boost of the intestinal immune system and changes in gene expression (barrier and endocrine functions, volatile fatty acids receptors) at hypothalamic and striatal levels and with changes in hippocampal and plasma metabolomic profiles. Some components present in HM (e.g.: oligosaccharides, non-protein nitrogen such as urea, bacteria consortia) and absent in IF can explain the discrepancies observed. IF-supplementation with these bioactive components and/or with the modulation of the protein profile would be of interest for further investigation
5
De, Vadder Filipe. « Détection portale des nutriments et contrôle de l'homéostasie énergétique par l'axe nerveux intestin-cerveau ». Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-01058661.
Texte intégralRésumé :
La production endogène de glucose est une fonction cruciale de l'organisme, permettant de maintenir l'homéostasie glycémique. Alors que la production accrue de glucose par le foie a des effets délétères, la néoglucogenèse intestinale (NGI) exerce des effets bénéfiques sur l'équilibre métabolique de l'organisme. Les régimes hyperprotéiques sont connus pour leurs effets de satiété. Grâce à des travaux physiologiques et moléculaires chez le rat et la souris, nous montrons dans une première partie que l'effet bénéfique des régimes hyperprotéiques passe par une induction de la NGI. Lors de la digestion des protéines alimentaires, des di- et tripeptides sont libérés dans la veine porte. Ces molécules agissent comme des antagonistes des récepteurs μ-opioïdes de la veine porte, initiant un arc réflexe intestin-cerveau induisant la NGI et la satiété. Dans un deuxième temps, nous proposons un modèle rendant compte des effets bénéfiques des régimes riches en fibres, tels que l'amélioration de la sensibilité à l'insuline et l'induction de la dépense énergétique. Les fibres solubles sont fermentées par le microbiote intestinal, produisant des acides gras à chaîne courte (AGCC), acétate, propionate et butyrate, à l'origine des effets métaboliques observés. Nous montrons que le butyrate active directement les gènes de la NGI dans les entérocytes, et que le propionate se lie aux récepteurs FFAR3 dans le système nerveux périportal, initiant un mécanisme de communication entre l'intestin et le cerveau induisant la NGI. De plus, nous montrons que la modification de la composition du microbiote par les fibres alimentaires n'est pas suffisante en soi pour induire les effets bénéfiques en absence de NGI
6
Strati, Francesco. « The microbiota-gut-brain axis : characterization of the gut microbiota in neurological disorders ». Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/368893.
Texte intégralRésumé :
The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota.
First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota. Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance.
It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects. RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself. Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controls’ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host. Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.
7
Strati, Francesco. « The microbiota-gut-brain axis : characterization of the gut microbiota in neurological disorders ». Doctoral thesis, Università degli studi di Trento, 2017. http://hdl.handle.net/10449/38243.
Texte intégralRésumé :
The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota.
First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota.
Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance.
It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects.
RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself.
Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controls’ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host.
Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.
8
Strati, Francesco. « The microbiota-gut-brain axis : characterization of the gut microbiota in neurological disorders ». Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/1917/1/STRATI_PhD_thesis_R1_2017.01.13.pdf.
Texte intégralRésumé :
The human gut microbiota plays a crucial role in the functioning of the gastrointestinal tract and its alteration can lead to gastrointestinal abnormalities and inflammation. Additionally, the gut microbiota modulates central nervous system (CNS) activities affecting several aspect of host physiology. Motivated by the increasing evidences of the role of the gut microbiota in the complex set of interactions connecting the gut and the CNS, known as gut-brain axis, in this Ph.D. thesis we asked whether the gastrointestinal abnormalities and inflammation commonly associated with neurological disorders such as Rett syndrome (RTT) and Autism could be related to alterations of the bacterial and fungal intestinal microbiota.
First, since only few reports have explored the fungal component of the gut microbiota in health and disease, we characterized the gut mycobiota in a cohort of healthy individuals, in order to reduce the gap of knowledge concerning factors influencing the intestinal microbial communities. Next, we compared the gut microbiota of three cohorts of healthy, RTT and autistic subjects to investigate if these neurological disorders harbour alterations of the gut microbiota. Culture-based and metataxonomics analysis of the faecal fungal populations of healthy volunteers revealed that the gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. Different fungal species were isolated showing phenotypic adaptation to the intestinal environment. High frequency of azoles resistance was also found, with potential clinical significance.
It was further observed that autistic subjects are characterized by a reduced incidence of Bacteroidetes and that Collinsella, Corynebacterium, Dorea and Lactobacillus were the taxa predominating in the gut microbiota of autistic subjects. Constipation has been associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by higher levels of Escherichia/Shigella and Clostridium cluster XVIII than constipated neurotypical subjects. RTT is a neurological disorder caused by loss-of-function mutations of MeCP2 and it is commonly associated with gastrointestinal dysfunctions and constipation. We showed that RTT subjects harbour bacterial and fungal microbiota altered from those of healthy controls, with a reduced microbial richness and dominated by Bifidobacterium, different Clostridia and Candida. The alterations of the gut microbiota observed did not depend on the constipation status of RTT subjects while this microbiota produced altered SCFAs profiles potentially contributing to the constipation itself. Phenotypical and immunological characterizations of faecal fungal isolates from RTT subjects showed Candida parapsilosis as the most abundant species isolated in RTT, genetically unrelated to healthy controls’ isolates and with elevated resistance to azoles. Furthermore these isolates induced high levels of IL-10 suggesting increased tolerance and persistence within the host. Finally, the importance of multiple sequence alignment (MSA) accuracy in microbiome research was investigated comparing three implementations of the widely used NAST algorithm. By now, different implementations of NAST have been developed but no one tested the performances and the accuracy of the MSAs generated with these implementations. We showed that micca, a new bioinformatics pipeline for metataxonomics data improves the quality of NAST alignments by using a fast and memory efficient reimplementation of the NAST algorithm.
9
Altera, Annalisa. « Gut-brain axis : the role of microbiota in gut and brain ageing ». Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1209555.
Texte intégralRésumé :
In the last decade there has been a growing interest in the reciprocal impact occurring between the gut and the brain and this is well conceptualized in the gut-brain axis notion. The gut-brain axis is the bidirectional communication route between the “little brain” (gut) and the “big brain” (brain). There are several factors that play an important role in this axis but it has become more and more evident that the gut bacteria represent a key component. This has led to the new concept of the microbiota-gut-brain axis, emphasizing the importance of the gut microbiota in this axis. The gut has evolved with bacteria in a symbiotic way and the human gut hosts about 1014 bacterial cells. Researches in the last years have highlighted the importance of the microbiota not only for gut functions but also for the central nervous system (CNS) development, physiology and pathology. However, there are different factors that influence the composition of the gut microbiota (mode of delivery, diet, stress and ageing). In particular, the composition of the gut microbiota changes with ageing: in the adults the majority of taxa are Bacteroidetes and Firmicutes while the elderly has a different composition of the gut microbiota. Some studies have reported a decrease in Bifidobacteria and an increase in Escherichia, Enterobacteriaceae and Clostridium difficile in the elderly. Interestingly, the centenarians apparently have no changes in gut microbiota in comparison to adult, further highlighting the importance of gut bacteria in longevity. Ageing is a physiological process related to the loss of function in different body systems and also associated with a decline in cognitive functions. It has become more and more evident that events taking place in the gut play a major role in the ageing process and in age-related diseases. Faecal microbial transplant (FMT) is a technique that consists in the transfer of gut microbiota from a donor to a recipient (usually via an oral gavage in rodents or colonoscopy in humans) and allows to establish a donor-like microbiota in the gastro-intestinal tract of the recipient. FMT is used to treat recurrent Clostridium difficile infections but there are studies trying to test this technique in the treatment of other pathologies such as irritable bowel syndrome, inflammatory bowel disease and constipation. It is also worth noticing that the
imbalance in the composition of the gut microbiota (dysbiosis) has been associated with a plethora of neurological disorders. In this context FMT is being investigated as a therapeutic option not only for treatment of gut disorders but also for diseases of the CNS. The present thesis illustrates a series of experiments by which we tested the impact of FMT from aged donor mice into young adult recipients. Controls were carried out operating FMT from young adult donor mice to age-matched recipients. Following transplantation, characterization of the microbiota and metabolomics profiles along with a series of cognitive and behavioural tests were carried out. Label-free quantitative proteomics was employed to evaluate protein expression in the hippocampus and gut after the transplant.
In addition, in the attempt to elucidate the mechanisms underlying microbiota-host interactions within the framework of the gut-brain axis, we worked on setting up a procedure to tracking down and visualize bacterial metabolites (such as peptides and lipids) that are thought to play a role acting as signaling molecules. To this end, we used copper-catalysed azide-alkyne cycloaddition (CuAAC) click chemistry, a biorthogonal reaction of widespread utility throughout medical chemistry and chemical biology. We sought to optimize click-based protocols to detect the production of lipids in gut-bacteria to track the metabolism of active bacterial cells. This technique use click chemistry to stain synthetic (e.g., noncanonical) precursors incorporated into bacterial cell biomass. After incorporation, the artificial molecules can be fluorescently detected via azide-alkyne reaction and visualized by confocal microscopy.
FMT from aged mice into adult recipients affected spatial learning and memory while we did not observe effects on locomotion and explorative behaviour. Alongside, there was an alteration in the expression of proteins related to synaptic plasticity and neurotransmission in the hippocampus which was not observed in controls. FMT from aged into young adult mice did not induce a significant increase in glial fibrillary acidic protein expression in hippocampal astrocytes suggesting the lack of an overt neuroinflammatory response. On the other hand, a significant increase in the expression of F4/80, a typical trait of the ageing brain, was observed in microglial cells resident in the fimbria. Gut permeability and levels of systemic and local (hippocampus, gut) cytokines were not affected. As regards click chemistry, we used
Bacteroides thetaiotaomicron grown in minimal medium supplemented with palmitic acid alkyne (PAA) and stained this molecule using an azide-containing fluorescent dye. After palmitic acid staining, co-culture experiments were performed to assess the transfer of this bacterial product to eukaryotic cell lines (CaCo2 and SK-N-SH cell lines). The successful transfer to host cells was confirmed by confocal microscopy. Results obtained in FMT experiments highlighted the importance of the gut microbiota on protein expression and functions of CNS. These results support the key role of microbiota in gut-brain axis and it would be of great importance to get more insight into the restoration of a young microbiota in the elderly to try to improve cognitive functions and the quality of life. Click chemistry experiments demonstrate that this technique could be employed to track molecules produced by gut bacteria to unveil their role in host-microbe interactions.
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Gorard, David A. « Intestinal motor function and the brain-gut axis in irritable bowel syndrome ». Thesis, Imperial College London, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395770.
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Lowe, Patrick P. « Inebriated Immunity : Alcohol Affects Innate Immune Signaling in the Gut-Liver-Brain Axis ». eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/987.
Texte intégralRésumé :
Alcohol is a commonly consumed beverage, a drug of abuse and an important molecule affecting nearly every organ-system in the body. This project seeks to investigate the interplay between alcohol’s effects on critical organ-systems making up gut-liver-brain axis.
Alcohol initially interacts with the gastrointestinal tract. Our research describes the alterations seen in intestinal microbiota following alcohol consumption in an acute-on-chronic model of alcoholic hepatitis and indicates that reducing intestinal bacteria using antibiotics protects from alcohol-induced intestinal cytokine expression, alcoholic liver disease and from inflammation in the brain. Alcohol-induced liver injury can occur due to direct hepatocyte metabolic dysregulation and from leakage of bacterial products from the intestine that initiates an immune response. Here, we will highlight the importance of this immune response, focusing on the role of infiltrating immune cells in human patients with alcoholic hepatitis and alcoholic cirrhosis. Using a small molecule inhibitor of CCR2/CCR5 chemokine receptor signaling in mice, we can protect the liver from damage and alcohol-induced inflammation. In the brain, we observe that chronic alcohol leads to the infiltration of macrophages in a region-specific manner. CCR2/CCR5 inhibition reduced macrophage infiltration, alcohol-induced inflammation and microglial changes. We also report that chronic alcohol shifts excitatory/inhibitory synapses in the hippocampus, possibly through complement-mediated remodeling. Finally, we show that anti-inflammasome inhibitors altered behavior by reducing alcohol consumption in female mice.
Together, these data advance our understanding of the gut-liver-brain axis in alcoholism and suggest novel avenues of therapeutic intervention to inhibit organ pathology associated with alcohol consumption and reduce drinking.
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Andersson, Jonas. « Is there a Connection Between the Gut-Microbiota and Major Depression ? » Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19150.
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Major depressive disorder (MDD) is rapidly growing and one of the most common causes of disability and mortality worldwide. People with MDD often display brain changes such as adisrupted balance in neurotransmitters, impaired neurogenesis and neuroplasticity. Traditionally has MDD been treated with medications and talking therapies (psychotherapy). Studies have shown that just around 50 % of people with MDD get improvements from common traditional treatments.Therefore is there a great need for a better understanding of MDD and new treatments. There is now an emerging field of research that indicates that the gut microbiota plays a crucial role in disturbing normal brain functioning in MDD. This connection between the gut and the brain is called the gutbrain axis.The thesis aims to investigate if there is a connection between gut microbiota disruption and MDD and if gut microbiota restoration can be a potential effective future treatment for MDD. Key findings of the thesis were, studies show that people with MDD often display gut microbiota disruption and chronic low grade inflammation. Studies also indicate that this inflammation can cause the specific brain change often displayed in people with MDD. One of the most critical findings in the thesis was that gut brain treatments affect tryptophan metabolism, which affects the risk of MDD. The research area of the gut brain axis is still new and many more studies are needed,particularly in humans.
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Murray, Emma. « Immune Challenge During Puberty : Role of the Gut Microbiota and Neurobehavioural Outcomes ». Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/40467.
Texte intégralRésumé :
Puberty is a critical period of development characterized by rapid physiological changes and significant brain reorganizing and remodeling. These rapid changes render the developing brain particularly vulnerable to stress and immune challenge. In mice, exposure to an immune challenge (lipopolysaccharide; LPS) during puberty causes enduring effects on stress reactivity, cognitive functioning, and depression- and anxiety-like behaviors later in life. However, the mechanisms underlying these effects are unknown. The gut microbiome can profoundly influence the immune system. There is also close bidirectional communication between the gut microbiome and the central nervous system (CNS) through neural, endocrine and immune signaling pathways, which can alter brain chemistry and emotional behaviour. Thus, we hypothesized that altering microbial composition during puberty could mitigate acute immune responses and prevent enduring outcomes later in life. The current thesis examined the effect of gut manipulation with probiotics during puberty on LPS-induced immune responses and enduring anxiety- and depression-like behaviours, and stress-reactivity in adulthood, in male and female CD1 mice (Article 1). Next, we examined age and sex differences in gut microbial composition before and after exposure to an immune challenge. We also examined the effects of consuming a single strain probiotic bacterium (Lactobacillus Reuteri) during puberty on the immune response and the long-term changes in memory, anxiety-like behavior, and stress reactivity in adulthood (Article 2). Lastly, we examined how microbial colonization between pubertal and adult mice can alter acute peripheral and central inflammatory responses to LPS (Article 3). The current dissertation has addressed sex-specific vulnerabilities to an immune challenge during pubertal development and the moderating influence of the gut microbiome. These studies have demonstrated that manipulating the gut microbiome during puberty can mitigate acute immune responses and prevent enduring neurobehavioural outcomes later in life.
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PALADINO, Letizia. « THE GUT-BRAIN AXIS : EFFECTS OF THE PROBIOTIC LACTOBACILLUS FERMENTUM INTRODUCED IN THE DIET OF ETHANOL-FED MICE ». Doctoral thesis, Università degli Studi di Palermo, 2022. https://hdl.handle.net/10447/563684.
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Hoffman, Jared D. « THE PREBIOTIC INULIN BENEFICIALLY MODULATES THE GUT-BRAIN AXIS BY ENHANCING METABOLISM IN AN APOE4 MOUSE MODEL ». UKnowledge, 2018. https://uknowledge.uky.edu/pharmacol_etds/24.
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Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the gut, periphery, and in the case of scyllo-inositol, the brain. We found in E3FAD and E4FAD mice fed either a prebiotic or control diet for 4-months, that the consumption of the prebiotic inulin can beneficially alter the gut microbiota, modulate metabolic function, and dramatically increase scyllo-inositol in the brain. This suggests that the consumption of prebiotics can beneficially impact the brain by enhancing metabolism, helping to decrease AD risk factors.
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Nilsson, Malin. « Effects of the Mediterranean Diet on Brain Function : Underlying mechanisms ». Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17531.
Texte intégralRésumé :
The Mediterranean diet (Medi) has been highlighted as the golden diet rich in protective properties associated with cognitive- and emotional health. The foundation of the Medi comprises vegetables, fruits, nuts and seeds, legumes, and extra virgin olive oil. Research has been conducted in both holistic dietary approach and single nutrient approach regarding the impact of nutrition and diet, in this case, the Medi‟s effect on brain health. This review aims to give an up to date overview of the Mediterranean diet, outline some of the diet's abundant nutrients, and discuss studies linking the nutrient's potential effect on depression, cognitive decline, dementia, and brain structure and function. In addition, this review will attempt to assess whether the Medi as a whole or if a single nutrient approach is accountable for the health-promoting findings. Furthermore, the gut-brain axis, and other potential underlying mechanisms involved in the modulation of food- and nutrient intake and their effects on the brain, will be outlined. A diet high in fruit-, vegetable-, polyunsaturated fatty acid-, and monounsaturated fatty acid content has great power for health-maintenance and decreases the risk of suffering cognitive decline, dementia, and potentially depression. More randomized controlled trials are however eagerly awaited to give more substance to previous findings.
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Lebovitz, Yeonwoo. « Modulation of Neurodevelopmental Outcomes using Lactobacillus in a Model of Maternal Microbiome Dysbiosis ». Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/94328.
Texte intégralRésumé :
Neurodevelopmental disorders, such as autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder, are a heterogeneous set of developmental disorders affecting the central nervous system. Studies into their etiology remain challenging, as neurodevelopmental disorders frequently present with a wide range of biological, behavioral, and comorbid symptomologies. Increasing epidemiological reports of antibiotic use during pregnancy as a significant correlate of subsequent mental disorder diagnosis in children suggest a mechanism of influence via the maternal gut-fetal brain axis. Importantly, antibiotics cause dysbiosis of the gut microbiome and disrupt the delicate composition of the microbial inoculum transferred from mother to child, which is critical for development of the immune system and holds implications for long-term health outcomes. The research objective of this dissertation is to reveal a causal mechanism of maternal microbial influence on neurodevelopment by examining the brain's resident immune cells, microglia, and corresponding behavioral outcomes in a mouse model of antibiotics-driven maternal microbiome dysbiosis (MMD). We identify early gross motor deficits and social behavior impairments in offspring born to MMD dams, which paralleled hyperactivated microglia in brain regions specific to cognition and social reward. The MMD microglia also exhibited altered transcriptomic signatures reflective of premature cellular senescence that support evidence of impaired synaptic modeling found in MMD brains. We report that these deficits are rescued in the absence of Cx3cr1, a chemokine receptor expressed ubiquitously on microglia, to highlight a pathway in which maternal microbiota may signal to neonatal microglia to undergo appropriate neurodevelopmental actions. Finally, we characterize Lactobacillus murinus HU-1, a novel strain of an important gut bacterium found in native rodent microbiota, and demonstrate its use as a probiotic to restore microglial and behavioral dysfunction in MMD offspring.Ph. D.
Population studies on neurodevelopmental disorders, such as autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder, highlight antibiotic use during pregnancy as a major correlate of subsequent diagnoses in children. These findings support a growing body of evidence from animal and human studies that the microbial ecosystems (“microbiome”) found in and on our bodies play significant roles in mental health, including mood, cognition, and brain function. Importantly, antibiotics during pregnancy create an imbalance of the gut microbiome (“dysbiosis”) and disrupt the microbial inoculum transferred from mother to child, which is critical for maturation of the infant immune system and holds implications for long-term health outcomes. Thus, the research objective of this dissertation is to identify a mechanism of influence from the mother’s gut to the neonate’s brain by examining the brain’s resident immune cells (“microglia”) in a mouse model of antibiotics-driven maternal microbiome dysbiosis (MMD). We uncover autism-like behavioral deficits and dysfunctional microglia in MMD offspring, and characterize signaling cues specific to microglia by which improper neurodevelopment may be taking place. We also reveal that the detrimental effects of MMD are reversed in mice born to mothers pretreated with a probiotic candidate, Lactobacillus murinus HU-1, to suggest maternally-derived Lactobacillus may help to mediate proper neurodevelopment.
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Lauffer, Adriana. « Efeito do estresse agudo, crônico e ambos combinados na permeabilidade intestinal de ratos ». reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/143409.
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Introdução: o estresse psicológico aumenta a permeabilidade intestinal em roedores e humanos, potencialmente levando a inflamação de baixo grau e aos sintomas em distúrbios gastrintestinais funcionais. No entanto, o efeito do estresse agudo combinado ao estresse da vida crônica, que mimetiza potencialmente melhor a situação humana, é desconhecido. Além disso, há poucos dados disponíveis sobre os efeitos do estresse em intestino delgado versus cólon. Métodos: ratos Wistar foram alocados em quatro protocolos de estresse: 1/ controles; 2/ estresse agudo (isolamento e movimentos limitados); 3/ Crowding stress:crônico e 4/ estresse agudo + estresse crônico. Amostras de jejuno e cólon foram colhidas para estudar a permeabilidade em câmaras deUssing, a expressão gênica de moléculas de junção firmes e a densidade de mastócitos. Níveis de corticosterona no plasma foram medidos. Principais resultados:corticosterona plasmática foi avaliada nas três condições de estresse, teve níveis mais altos na condição de estresse combinado. Permeabilidade do jejuno foi aumentada em todas as condições de estresse e correlacionada com os níveis de corticosterona. O aumento da expressão das claudinas 1, 5 e 8, daocludina e da ZO-1 foi detectado no estado de estresse agudo no jejuno. Em contraste, a permeabilidade do cólon foi aumentada no protocolo de estresse combinado, e a expressão de moléculas das junção firmes permaneceu inalterada. O aumento da densidade de mastócitos foi observado no cólon nos ratos submetidos aos estresses crônico e combinado. Conclusão e inferências:os estresses agudo, crônico e combinado influenciam diferentemente a permeabilidade intestinal, a expressão de moléculas de junção firmes e a atividade dos mastócitos, no jejuno e no cólon. Estes resultados fornecem uma visão mais aprofundada dos mecanismos de hiperpermeabilidade intestinal relacionadas ao estresse.Background: Psychological stress increases intestinal permeability in rodents and humans, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders through disturbances in brain-gut axis. However, the effect of acute stress on the background of Crhonic life stress, potentially better approaching the human situation, is unknown. Moreover, only limited information is available on the effects in small intestine versus colon in animal model. Methods: Wistar rats were allocated to 4 stress protocols: 1/ sham; 2/ acute stress (isolation and limited movement); 3/ Crhonic crowding stress and 4/ acute + Crhonic stress (n = 8 per group). Jejunum and colon were harvested to study permeability in Ussing chambers, gene expression of tight junction molecules and mast cell density. Plasma corticosterone levels were measured. Key Results: Plasma corticosterone was elevated in all three stress conditions, with the highest levels in the combined stress condition. Permeability of the jejunum was increased in all stress conditions and correlated with corticosterone levels. Increased expression of claudin 1, 5 and 8, occludin and ZO-1 was detected in the acute stress condition in the jejunum. In contrast, colonic permeability was increased in the acute on Crhonic stress protocol only and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the Crhonic and acute on Crhonic stress condition in the colon only. Conclusion and Inferences: Acute, Crhonic and combined stress differentially affect intestinal permeability, expression of tight junction molecules and mast cells in the jejunum and the colon. These findings provide further insight in the mechanisms of stress-related intestinal hyperpermeability and barrier.
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Jaglin, Mathilde. « Axe intestin-cerveau : effets de la production d’indole par le microbiote intestinal sur le système nerveux central ». Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112312/document.
Texte intégralRésumé :
Le tube digestif héberge une communauté microbienne complexe, le microbiote intestinal, dont les capacités métaboliques sont plus riches et diversifiées que celles codées par le génome de l'hôte. L'implication du microbiote intestinal dans divers aspects de la physiologie de l'hôte, comme le métabolisme nutritionnel et l'immunité, est depuis longtemps étudiée. En revanche, l'action potentielle du microbiote sur le développement et le fonctionnement du cerveau constitue une nouvelle piste de recherche, encore peu explorée. Dans ce contexte, nous avons réalisé une première étude générale de l'action du microbiote intestinal sur le cerveau en comparant les fonctions sensori-motrices, le comportement de type anxieux, l'état d'activation de l'axe hypothalamo-hypophyso-surrénalien et le profil cérébral des monoamines de rats F344 axéniques et conventionnels. Les résultats révèlent que, chez cette lignée particulièrement sensible au stress, l'absence de microbiote intestinal exacerbe le comportement de type anxieux et la réponse hormonale au stress, et atténue le métabolisme dopaminergique cérébral. Afin d'étudier par quel moyen le microbiote peut agir sur le cerveau, une seconde étude a été menée, ciblant un métabolite bactérien spécifique, l’indole, dont certains dérivés oxydés par le foie sont connus pour avoir des propriétés neuroactives. L'indole est un métabolite naturel du microbiote intestinal, dont la surproduction pourrait survenir lors d'une dysbiose du microbiote. Deux cas de surproduction ont été modélisés : chronique et aiguë. Dans les deux cas, des modifications importantes du comportement de l'hôte ont été observées. En situation de surproduction chronique, l'indole favorise des comportements de type anxieux et dépressif, tandis qu'une surproduction aiguë a un effet sédatif marqué. D'un point de vue mécanistique, nous confirmons que l’indole peut agir sur le système nerveux central par la voie sanguine impliquant les dérivés oxydés et montrons pour la première fois qu'il peut aussi agir en activant les noyaux cérébraux du nerf vagueThe gastro-intestinal tract hosts a complex microbial community, the gut microbiota, whose collective genome coding capacity vastly exceeds that of the host genome. The involvement of the gut microbiota in various aspects of the host physiology, such as the nutritional metabolism and the immunity, has long been studied. In contrast, the possible action of the gut microbiota on brain development and functioning is a new line of research, still poorly explored. In this context, we performed a first general study of the effect of gut microbiota on the brain by comparing the sensory-motor functions, the anxiety-like behaviour, the activation of the hypothalamic-pituitary-adrenal axis and the brain monoamine profile in germ-free and conventional F344 rats. The results show that, in this particularly stress-sensitive strain, absence of gut microbiota exacerbates the anxiety-like behaviour and neuroendocrine response to stress, and reduces brain dopamine metabolism. To investigate the means by which the microbiota can affect the brain, a second study was conducted, targeting a specific bacterial metabolite, indole, whose oxidative derivatives, produced by the liver, are known to have neuroactive properties. Indole is a natural metabolite of the gut microbiota, whoseoverproduction could occur during a microbiota dysbiosis. Two conditions of overproduction, namely chronic and acute, were modelled. In both cases, significant changes in the behaviour of the host were observed. In chronic overproduction, indole promotes anxiety- and depressive-like behaviours, while acute overproduction has a marked sedative effect. From a mechanistic point of view, we confirm that indole can act on the central nervous system through its oxidized derivatives and show for the first time that it can also act by activating the brain nuclei of the vagus nerve
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Eckered, Göransson Sara. « Kan probiotika lindra depression ? » Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-84831.
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Tidigare forskning har visat ett samband mellan vår tarmflora och vår fysiska hälsa, och idag görs även mycket forskning på om den även kan påverka vår mentala hälsa. Idag lider över fyra procent av världens befolkning av depression, och den här litteraturstudien har, genom att analysera sju studier och deras resultat, försökt få svar på frågan om probiotika kan lindra depression. Antingen som primär behandling eller som komplement till annan behandling. Den här litteraturstudien gav inga konkreta svar på den frågan, annat än att alla inblandade forskare är överens om att det behövs göra fler, längre och större studier innan man kan dra några slutsatser.Previous research has shown a connection between our microbiota and physical health, and today a lot of research is also being done on whether it also can affect our mental health. Today, over four percent of the world's population suffers from depression, and this literature study has, by analysing seven studies and their results, attempted to answer the question of whether probiotics can alleviate depression. Either as primary treatment or as a supplement to other treatment. This literature study did not provide any definite answers to that question, other than that all the researchers involved in the studies analysed agree that more, longer and larger studies are needed before one can draw any conclusions.
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Roque, Ana Filipa Silva. « Internship Reports and Monograph entitled "The Influence of Gut Microbiota in the Development of Schizophrenia" ». Master's thesis, 2020. http://hdl.handle.net/10316/93120.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaO microbiota intestinal humano é constituído por um vasto número de microrganismos,maioritariamente bactérias, que se co-desenvolveram com o seu hospedeiro humano.Recentemente, neurocientistas começaram a apreciar a influência da interação dinâmica entreos micróbios intestinais e os sistemas gastrointestinal e nervoso do seu hospedeiro,atualmente conhecido por eixo microbiota-intestino-cérebro. Esta comunicação bidirecionalenvolve vias imunológicas, neuronais, endócrinas e metabólicas. Evidências de estudosrealizados nos últimos anos sugerem que o microbiota pode estar associado a doençasneuropsiquiátricas, em particular a esquizofrenia.Esta monografia resume e discute as informações atualmente disponíveis sobre ainfluência do ambiente gastrointestinal no sistema nervoso central, com foco no eixomicrobiota-intestino-cérebro, os mecanismos subjacentes à comunicação bidirecional entre omicrobiota intestinal e o cérebro, o impacto que o eixo microbiota-intestino-cérebro podeter na esquizofrenia e novas estratégias terapêuticas, de modo a estabelecer perspetivas parao futuro. Com efeito, estudos recentes relataram que distúrbios neuropsiquiátricos, como aesquizofrenia estão associados a alterações do microbiota intestinal, um fenómeno conhecidopor disbiose. Alterações no microbiota intestinal induzem a ativação anormal das principaisvias de comunicação do eixo microbiota-intestino-cérebro através de mecanismosimunológicos, neurais, endócrinos, metabólicos e epigenéticos, levando a uma inflamaçãoexacerbada da mucosa intestinal e a alterações nas respostas ao stress.Em jeito de conclusão, o eixo microbiota-intestino-cérebro emerge agora como umanova estratégia terapêutica para prevenção e tratamento de distúrbios neuropsiquiátricos,incluindo a esquizofrenia. No entanto, mais estudos são necessários para que a visãotradicional da etiologia das doenças neuropsiquiátricas seja alterada, revelando o papel real doeixo microbiota-intestino-cérebro e o seu potencial como alvo de novos tratamentos.
The human gut microbiota (GM) comprise a large number of microorganisms, mostlybacteria, which co-evolved together with their human host. Recently, neuroscientist began toappreciate the influence of the dynamic interaction between gut microbes and hostgastrointestinal and central nervous system, the now known microbiota-gut-brain (MGB) axis.This bidirectional communication involves immune, neural, endocrine and metabolic pathways.Recent evidences suggest that microbiota may be associated with the pathogeny ofneuropsychiatric diseases, in particular schizophrenia (SCZ).This document summarizes and discusses currently available information on theinteraction between the gastrointestinal and central nervous system, focusing on the MGBaxis, the mechanisms underlying the bidirectional communication between the GM and thebrain, the impact that MGB axis may have in SCZ and novel therapeutic strategies, to establishfuture perspectives. Indeed, recent studies reported that neuropsychiatric disorders, such asSCZ, are associated with changes in the GM, a phenomenon known as dysbiosis. Alterationsin the GM induce aberrant activation of key pathways of MGB axis communication, includingimmune, neural, endocrine, metabolic and epigenetic mechanisms, leading to exacerbatedintestinal mucosal inflammation and altered responses to stress.The MGB axis may provide a novel therapeutic strategy for the prevention andtreatment of neuropsychiatric disorders, including SCZ. However, further research is requiredto change the traditional view of neuropsychiatric diseases, revealing the feasibility andpotential of the of MGB axis as a target for novel treatment.
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Centeio, Rita Correia. « Relatórios de Estágio e Monografia intitulada "Papel da Microbiota Intestinal nas Perturbações do Espetro do Autismo" ». Master's thesis, 2021. http://hdl.handle.net/10316/99120.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaAs Perturbações do Espetro do Autismo englobam um conjunto de distúrbios do neurodesenvolvimento. A fisiopatologia desta doença é muitas vezes idiopática, podendo ocorrer devido a predisposição genética, fatores ambientais, ou ainda, resultar da interação dos dois. Tem como consequência défices na comunicação e interação social, comportamentos anormais, estereotipados e repetitivos e, com grande prevalência, sintomas gastrointestinais. Está comprovado que a microbiota intestinal tem impacto em inúmeras funções imunológicas, metabólicas e neuronais, através da comunicação bidirecional entre o cérebro e o intestino, denominada eixo intestino-cérebro. Vários estudos demonstram que o intestino tem a capacidade de influenciar o desenvolvimento do cérebro. Assim, surgiu a hipótese de que a disbiose intestinal pudesse estar implicada na fisiopatologia desta doença. A composição alterada da microbiota pode modular as vias de interação entre a microbiota e o sistema nervoso central, o que vai originando consequências a nível comportamental e cognitivo, e por sua vez originando diferentes fenótipos da doença. Simultaneamente, terapêuticas que têm como objetivo restabelecer o equilíbrio da microbiota apresentam efeitos benéficos na diminuição da severidade e correção dos comportamentos destes doentes. Neste documento é feita uma análise à alteração das vias de comunicação do eixo intestino-cérebro, qual a influência que a disbiose exerce nas mesmas, e como é que a modulação do intestino pode ser benéfica para o doente com perturbação do espetro do autismo.
Autism Spectrum Disorders encompass a set of neurodevelopmental disorders. The pathophysiology of this disease is often idiopathic and may occur due to genetic predisposition, environmental factors, or even result from the interaction of both. It results in deficits in communication and social interaction, abnormal, stereotyped, repetitive behaviors and interests, and, with great prevalence, gastrointestinal symptoms, like constipation and flatulence. It has been proven that the gut microbiota has an impact on numerous immune, metabolic and neuronal functions, through bidirectional communication between the brain and the intestine, called gut-brain axis. Several studies show that the intestine has the capacity to influence brain development. Thus, the hypothesis emerged that intestinal dysbiosis could be involved in the pathophysiology of this disease. The altered composition of the microbiota may modulate the interaction pathways between the microbiota and the central nervous system, leading to behavioral and cognitive consequences, and in turn different disease phenotypes. Simultaneously, therapies that aim to restore the balance of the microbiota have beneficial effects in reducing the severity and correcting the behavior of these patients. In this document, an analysis is made of the alteration of the communication pathways of the gut-brain axis, the influence that dysbiosis exerts on them, and how the modulation of the intestine can be beneficial to the patient with autism spectrum disorder.
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Soares, Raquel Araújo. « Influência da Microbiota Intestinal nas Perturbações do Espetro do Autismo ». Master's thesis, 2017. http://hdl.handle.net/10316/83643.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA microbiota intestinal é o conjunto dos microrganismos que existem no intestino humano, constituída maioritariamente por bactérias, mas também por fungos, vírus eprotozoários. O eixo microbiota-intestino-cérebro refere-se às interações entre o sistema nervoso central, o sistema gastrointestinal e os microrganismos que vivem no trato gastrointestinal, interações estas que se realizam via neural, endócrina, imunológica e metabólica. Alterações neste eixo, designadas de disbiose, podem provocar problemas de crescimento e desenvolvimento, incluindo o desenvolvimento do sistema nervoso central, os quais estão associados à etiologia de várias doenças, nomeadamente, as designadas por Perturbações do Espetro do Autismo. Problemas gastrointestinais estão intimamente relacionados com esta doença etratamentos com probióticos, antibióticos e alterações na dieta estão a ser estudados paraalívio destes sintomas.
The intestinal microbiota is the set of microorganisms that exist in the human intestine,consisting mainly of bacteria, but also by fungi,viruses and protozoa. The microbiota-intestine-brain axis refers to the interactions between the central nervous system, the gastrointestinal system and the microorganisms that live in thegastrointestinal tract. These interactions are carried out via neural,endocrine, immunological and metabolic. Changes in this axis, called dysbiosis,can lead to problems of growth and development, including the development of thecentral nervous system, which are associated with the etiology of various diseases,namely Autism Spectrum Disorders.Gastrointestinal problems are closely related tothis disease and treatments with probiotics,antibiotics and changes in diet arebeing studied to relieve these symptoms.
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Queiroz, João Pedro Nunes. « O microbiota e o ser humano ». Master's thesis, 2017. http://hdl.handle.net/10316/83633.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaO ser humano coexiste com as mais diversas espécies bacterianas. Esta coexistência dá-se devido aos benefícios mútuos existentes para ambos, a espécie humana fornecendo nutrientes necessários à sobrevivência das espécies bacterianas e estas contribuindo para o nosso desenvolvimento, nomeadamente auxiliando no desenvolvimento do SNC e do Sistema imunitário. Estas espécies que colonizam o intestino, a pele e diversas mucosas como a nasal, bocal, vaginal e pulmonar constituem o microbiota que é, portanto, o conjunto das espécies associadas a uma determinada região. O conjunto das interações entre o microbiota e o seu habitat denomina-se microbioma.Neste trabalho irei abordar vários tipos de microbiota existentes no corpo humano dando especial ênfase ao microbiota intestinal e a modulação deste. O microbiota intestinal é composto por diversos microrganismos incluindo bactérias, fungos, protozoários e vírus. Estima-se que cada indivíduo contenha mais de 100 espécies diferentes no seu trato gastrointestinal e que estas sejam compostas por um total de 10!" − 10!" células, o que representa um número cerca de dez vezes maior que o representado pelas células eucariotas. Também será abordado os efeitos que fatores externos como probióticos, prebióticos, antibióticos e fatores internos como o Brain Gut Axis, sistema imunitário e nervoso têm neste. Por fim irei referir o potencial impacto clinico que o microbiota e o desequilíbrio deste (disbiose) poderão ter na doença de Parkinson, na malária e um novo método clínico de diagnóstico, que procura padronizar o microbiota e a partir disso traçar o perfil dele, permitindo facilmente identificar períodos de disbiose. Isto por sua vez é um passo na criação de uma infraestrutura necessária para no futuro poder utilizar o microbiota como uma estratégia de diagnóstico, para a monitorização de regimes terapêuticos prescritos e para a melhoria de novas aproximações terapêuticas.
The human being coexists with the most diverse bacterial species. This coexistence is due to the mutual benefits existing for both. The human species provides nutrients necessary for the survival of bacterial species and these contribute to our development, assisting in the development of the CNS and the immune system. These species that colonize the intestine, the skin and various mucosae such as nasal, mouth, vaginal and pulmonary establish the microbiota, which is the group of species associated to a certain region. The set of interactions between the microbiota and its habitat is called microbiome.In this work, I will address several types of microbiota in the human body with special emphasis on the intestinal microbiota and its modulation. The intestinal microbiota is composed of several microorganisms including bacteria, fungi, protozoa and viruses. It is estimated that each individual contains more than 100 different species in their gastrointestinal tract and that these are composed by a total of 10!" − 10!" cells, representing a number ten times greater than the one represented by eukaryotic cells. We will also address the effects that external factors such as probiotics, prebiotics, antibiotics and internal factors such as the Brain Gut Axis, immune and nervous system have in the microbiota. Finally, I will mention the potential clinical impact that the microbiota and its imbalance (dysbiosis) may have on Parkinson's disease, malaria and a new clinical diagnostic method, which seeks to standardize the microbiota and from there to outline its profile, allowing to easily identify periods of dysbiosis. This is a necessary step in creating an essential infrastructure for the future use of the microbiota as a diagnostic strategy, for the monitoring of prescribed therapeutic regimens and for the improvement of new therapeutic approaches.
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Sacramento, Maria João de Sousa. « Relatórios de Estágio e Monografia intitulada “A Influência da Microbiota Intestinal nas Doenças Neurodegenerativas” ». Master's thesis, 2020. http://hdl.handle.net/10316/93008.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaThe gastrointestinal tract harbours a complex and dynamic community of microorganisms, collectively called the gut microbiota. The gut microbiota coexists on a symbiotic relationship with the human host and is responsible for a wide range of physiological functions that ensure individual health and homeostasis.The gut microbiota is a living ecosystem whose composition may be perturbed, resulting in a misplaced and eventually pathogenic profile, known as dysbiosis. This dysregulation is associated with the development and progression of many diseases, including neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.In the last few years, several mechanisms have been proposed to explain the implications of the gut microbiota in the central nervous system. The microbiota-gut-brain axis is a bidirectional system between the central nervous system and the gastrointestinal tract. This communication system is mainly composed by four dynamic communication pathways: nervous, endocrine, immune and metabolic.Based on this interaction some alternative therapeutics with potential impact on the prevention of neurodegenerative diseases have been proposed, including probiotics, prebiotics, symbiotics, antibiotics, diet and fecal microbiota transplantation.The main purpose of this dissertation is to debate the role of the intestinal microbiota as a possible conditioning factor in the pathophysiology of neurodegenerative diseases, in particular Alzheimer’s and Parkinson’s diseases.
O trato gastrointestinal alberga uma complexa e dinâmica comunidade de microorganismos, denominada por microbiota intestinal. A microbiota intestinal coexiste numa relação simbiótica com o hospedeiro humano e é responsável por exercer uma série de funções essenciais para a saúde e homeostase do indivíduo.A microbiota intestinal é um ecossistema vivo capaz de sofrer perturbações na sua composição, o que poderá resultar num perfil desajustado e eventualmente patogénico, designado por disbiose. Esta desregulação da microbiota intestinal contribui para o desenvolvimento e progressão de diversas doenças, nomeadamente doenças neurodegenerativas, das quais se destacam a doença de Alzheimer e a doença de Parkinson. Nos últimos anos, têm sido propostos vários mecanismos com o intuito de explicar as implicações que a microbiota intestinal pode ter no sistema nervoso central. Surge assim, o conceito do eixo microbiota-intestino-cérebro, que é um sistema de comunicação bidirecional entre o sistema nervoso central e o trato gastrointestinal. A comunicação entre a microbiota, o intestino e o cérebro é assegurada por quatro vias de comunicação dinâmicas, as vias neuronal, endócrina, imunológica e metabólica. Com base nesta interação, têm sido propostas alternativas terapêuticas com potencial impacto na prevenção das doenças neurodegenerativas, nomeadamente probióticos, prebióticos, simbióticos, antibióticos, dieta e transplante de microbiota fecal.O principal objetivo desta monografia é discutir o papel da microbiota intestinal como um possível fator condicionante na fisiopatologia das doenças neurodegenerativas, em particular nas doenças de Alzheimer e de Parkinson.
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Martins, André Magno de Sá Vieira. « Transplante fecal, o seu impacto na microbiota intestinal e opções terapêuticas associadas ». Master's thesis, 2020. http://hdl.handle.net/10316/97751.
Texte intégralRésumé :
Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de MedicinaA microbiota intestinal tem sido uma das temáticas mais intensamente exploradas pela comunidade científica, nas últimas duas décadas. O termo “microbiota intestinal” refere-se a uma vasta comunidade composta por milhões de microorganismos, essencialmente bactérias, que se relacionam entre si, com o organismo hospedeiro e com o meio externo.No decorrer dos últimos anos, foram vários os estudos que atribuíram à microbiota intestinal funções integrantes da modulação do sistema imunitário, génese de estados pró-inflamatórios e produção de diversas proteínas, entre as quais algumas com função neuromoduladora. Consequentemente, verificou-se um crescente interesse no conhecimento do seu papel em várias patologias gastointestinais, metabólicas, neuropsiquiátricas e autoimunes. Define-se transplante de microbiota intestinal como a transferência de material fecal de um sujeito dador, aparentemente saudável, para um sujeito recetor com um desequilíbrio manifesto na sua comunidade microbiótica intestinal. Potencialmente, em tese, este último beneficiará que o seu aparelho gastrointestinal seja colonizado pela microbiota do dador. Atualmente este procedimento já está aprovado para o tratamento da infeção por C. difficile recorrente ou refratária à terapêutica standard, mas prevê-se que o seu espectro de ação possa ser ampliado para diversas outras patologias. Este artigo de revisão aborda o conceito de transplante de microbiota fecal, a sua forma de administração, efeitos adversos associados e potenciais doenças que possam beneficiar desta modalidade terapêutica. É ainda dado enfoque à fisiopatologia e aos mecanismos através dos quais este inovador procedimento pode ser benéfico.
In the last two decades, intestinal microbiota has been one of the most discussed issues by the scientific community. The term ”intestinal microbiota” refers to a vast community structure made up by millions of microorganisms, mostly bacteria, which interact with each other, with the host, and with the external environment as well. Over the last few years, several studies have associated intestinal microbiota with immune system modulation, generation of proinflammatory states and in the production of several proteins, including neuromodulators. Therefore, it has been an increasing interest to find out its role in gastrointestinal, metabolic, neuropsychiatric and autoimmune disorders. Faecal Microbiota Transplantation is the process of transferring faecal bacteria from a healthy individual into another individual who suffers from intestinal microbiota disorders. On paper, the latter will benefit from the transplant of the donor’s intestinal microbiota. Nowadays, this procedure is approved for the treatment of recurrent C. difficile or when standard treatment fails, but its action spectrum is expected to be expanded to other pathologies.This review addresses the concept of faecal microbiota transplantation, its therapeutical procedure, its adverse effects and the potential diseases whose treatment can benefit from the performance of this medical method. Moreover, it also focuses on physiopathology and the mechanisms through which this novel procedure can have a positive outcome.
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Ribeiro, Ricardo Manuel Esteves. « Innovative pathways underlying the etiology and the therapeutics via modulation of the gut microbiota ». Master's thesis, 2018. http://hdl.handle.net/10316/84748.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaUma vez que não existe cura definitiva para doença de Parkinson, a busca de alternativas terapêuticas e outros alvos terapêuticos sobressai como uma necessidade urgente na sociedade moderna.Estudos recentes, evidenciam uma íntima e complexa via de comunicação bidirecional entre o cérebro e o trato gastro-intestinal envolvendo o microbiota: o eixo cérebro-intestino-microbiota. Esta rede de comunicação entre o cérebro e o intestino pode ser o fator determinante na progressão de doenças neurodegenerativas, nomeadamente a doença de Parkinson. Tem sido demonstrado em vários trabalhos que alterações no microbiota intestinal desencadeia uma série de mecanismos celulares que levam a um processo inflamatório exagerado que, por sua vez, debilita a integridade do epitélio intestinal. Este desequilíbrio na permeabilidade do epitélio intestinal exacerba a resposta inflamatória a qual se propaga para o sistema nervoso entérico, contribuindo para a formação de agregados de α-sinucleína. Dada a ligação entre o sistema nervoso entérico e o sistema nervoso central, através do nervo vago, a inflamação e os agregados de α-sinucleína propagam-se até ao sistema nervoso central, onde ocorre deposição de agregados de α-sinucleína nos neurónios da substantia nigra. Contudo terapias alternativas à base de precursores de compostos fosfolipídicos, probióticos, prébióticos e simbióticos relavam um efeito neuroprotetor e anti-inflamatório, podendo assim representar uma nova abordagem a terapêutica da doença de Parkinson. Neste trabalho discute-se criticamente estas novas vias subjacentes à etiologia e à intervenção terapêutica na doença de Parkinson.
Since there is no definitive cure for Parkinson's disease, the search for therapeutic alternatives and other therapeutic targets stands out as an urgent need in modern society.Recent studies show an intimate and complex bi-directional communication pathway between the brain and the gut involving the microbiota: the microbiota-gut-brain axis. This communication network may be the determining factor in the progression of certain neurodegenerative diseases, namely Parkinson's disease. It has been shown by several studies that changes in the intestinal microbiota triggers a series of cellular mechanisms that lead to an exaggerated inflammatory process that weakens the integrity of the intestinal epithelium. This imbalance in the permeability of the intestinal epithelium exacerbates the inflammatory response which spreads to the enteric nervous system, contributing to the formation of α-synuclein aggregates. Due to the connection between the enteric nervous system and the central nervous system through the vagus nerve, inflammation and α-synuclein aggregates spread to the central nervous system, where occurs deposition of α-synuclein in the neurons of the substantia nigra. However, alternative therapies based on phospholipidic membrane precursors, probiotics, prebiotics and synbiotics relied on a neuroprotective and anti-inflammatory effect and could therefore represent a new approach to the treatment of Parkinson's disease. Here we critically address these novel and innovative pathways underlying both PD etiology and therapeutic intervention.
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Dias, Inês Marques de Matos. « "Impacto do Consumo de Alimentos Ricos em Polifenóis no Eixo Intestino-Cérebro na Doença de Parkinson" ». Master's thesis, 2018. http://hdl.handle.net/10316/84405.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA Doença de Parkinson (DP) é uma das doenças neurodegenerativas mais comuns, caracterizada pela perda de neurónios dopaminérgicos. É geralmente diagnosticada já numa fase avançada da doença, onde os doentes apresentam sintomas motores que diminuem significativamente a sua qualidade de vida, além de que dificulta o seu tratamentoA comunicação entre o trato gastrointestinal (GI) e o cérebro, denominada Eixo Intestino-Cérebro, parece estar correlacionada com o desenvolvimento e progressão da DP. Esta interação é possível através de várias vias: neuronal, endócrina, imune ou metabólica. Este conhecimento abre a possibilidade de novas formas de atuação na DP, através de estratégias que foquem o trato GI. Neste contexto, a utilização de alimentos ricos em polifenóis surge como uma alternativa terapêutica promissora. Estas moléculas estão especialmente presentes na dieta Mediterrânea, rica no consumo de frutos e vegetais. Estes compostos têm propriedades anti-inflamatórias e antioxidantes relevantes, bem como a capacidade de modular o microbioma intestinal, componentes críticos da comunicação intestino-cérebro e da patofisiologia da DP.A Doença de Parkinson (DP) é uma das doenças neurodegenerativas mais comuns. O diagnóstico da DP é realizado numa fase tardia, onde o doente apresenta sintomas motores (SM) graves e em que já há um elevado grau de neurodegeneração. Além disso, os fármacos utilizados não impedem a progressão da doença, apenas aliviam os SM. Assim, seria importante realizar um diagnóstico mais precoce e encontrar alternativas para a prevenção e tratamento da DP.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by the loss of dopaminergic neurons. It is usually diagnosed at an advanced stage of the disease, where patients have motor symptoms that significantly reduce their quality of life and make treatment difficult.Communication between the gastrointestinal tract (GI) and the brain, called the Gut-Brain Axis, seems to be correlated with the development and progression of PD. This interaction occurs through several pathways: neuronal, endocrine, immune or metabolic. This knowledge brings alternatives in PD management, using strategies that focus the GI tract.In this context, the use of polyphenol-rich food appears as a promising therapeutic alternative. These molecules are vastly present in the Mediterranean diet, due to fruit and vegetable consumption. These compounds have relevant anti-inflammatory and antioxidant properties as well as the ability to modulate the intestinal microbiome, critical components of GI-brain communication and the pathophysiology of PD.Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The diagnosis of PD is performed at a later stage, where the patient has severe motor symptoms (MS) and in which there is already a high degree of neurodegeneration. In addition, the drugs used do not prevent the progression of the disease, they only relieve MS. Thus, it would be important to carry out an earlier diagnosis and to find alternatives for the prevention and treatment of PD.
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Cusimano, Frank Anthony. « Engineered bacteria for the modulation of intestinal physiology, inflammation, and behavior along the microbiome-gut-brain axis ». Thesis, 2019. https://doi.org/10.7916/d8-97dx-7887.
Texte intégralRésumé :
Bacteria in the gastrointestinal tract play an important role in intestinal motility, inflammation, homeostasis, and behavior. Bacteria, through the natural synthesis of neuroactive compounds and secondary metabolites, can modulate the host immune system and communicate with the host along the signaling pathway along the gut-brain axis. Here, we functionally design, develop, test, and characterize a platform for the study of microbial-host interactions using advancements in the field of synthetic biology.
First, we describe the engineering of Escherichia coli Nissle to biosynthesize serotonin within the mammalian gut using a native-plasmid optimized approach. Serotonin is crucial for neurotransmission throughout the body and may be playing a role in microbial gut-brain communication. In the gastrointestinal tract, serotonin regulates intestinal motility, cell turnover, intestinal inflammation, and gastrointestinal homeostasis. Upon serial daily oral gavages, our engineered bacterium populates a murine colon to produce serotonin locally in the mucosa layers along the epithelial lining. Changes in host physiology were observed including decreased gastrointestinal motility, increased colonic Muc2 expression, induction of host TPH2, responsible for serotonin biosynthesis in enteric neurons, and upregulation of serotonin receptors HTR3, HTR4, and HTR7 in the colon. Behavioral tests revealed a statistically significant decrease in anxiety and depression in stress-induced environments in mice treated with the engineered bacterium. This work suggests that gut bacteria engineered to modulate host gut-brain axis may have both scientific and clinical uses to study microbial-host interactions and treat gastrointestinal and behavioral mood disorders in humans.
Second, we engineered bacteria to produce exogenous butyrate and other SCFAs in the murine gut. Short chain fatty acids (SCFAs) play an important role in intestinal homeostasis, fluid dynamics, inflammation, oxidative stress, and intestinal hypersensitivity and motility. With this development, we characterized the effects of our butyrate-producing bacteria on a high-fat diet and DSS-induced colitis model within the colon. Although energetically burdensome to produce, our strains produced butyrate in the colon at higher density in an actively inflamed colitis model. After 14 days of oral administration, our engineered strain (EcN:B) increased the colon length of normal wild-type mice, in high fat fed mice, and in mice with recovering and actively inflamed DSS-induced colitis. EcN:B increased mucosal barrier thickness, upregulated gene expression of the barrier integrity markers Cldn1, Ocln, Zo1, and altered crypt and villus height during inflammation recovery. Furthermore, as butyrate is known to induce Foxp3+ Regulatory T cells, we saw a 13.01% percent increase in Foxp3+ cells in the colon of mice fed our engineered bacteria. This work suggests that synthetic gut bacteria engineered to produce short chain fatty acids may have future clinical uses to treat patients with inflammatory bowel disease including Crohn’s and Colitis with future potential to serve as a therapeutic for irritable bowel syndrome, idiopathic constipation, obesity, and colorectal cancer.
This platform, with the use of synthetic biology to natively engineer Escherichia coli Nissle to produce bioactive compounds in the distal gastrointestinal tract, creates a framework for future characterization of bacterial-host communication and future microbial-based therapeutics.
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Cadima, Joana Catarina Pinto. « "O eixo microbiota-intestino-cérebro na Doença de Parkinson" ». Master's thesis, 2020. http://hdl.handle.net/10316/93079.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA Doença de Parkinson (DP) é uma doença neurodegenerativa caracterizada pela degeneração e morte dos neurónios dopaminérgicos na substância nigra pars compacta,acompanhada por sinucleinopatia.Vários estudos sugerem que a disfunção mitocondrial, o stress oxidativo, a neuroinflamação e a agregação da α-sinucleína desempenham um importante papel na neurodegeneração. No entanto, o que despoleta tais mecanismos e torna a neurodegeneração progressiva e descontrolada permanece largamente por esclarecer. Neste contexto,recentemente, surgiram evidências inovadoras de que a DP poderá ter início no intestino e que o microbiota intestinal, um importante modulador da complexa comunicação bidirecional que ocorre entre o cérebro e o sistema gastrointestinal (eixo microbiota-intestino-cérebro),exercerá um papel chave na patogénese desta doença neurodegenerativa.Dado a etiologia da DP não se encontrar ainda esclarecida, esta doença não tem cura,sendo fundamental desenvolver novas estratégias terapêuticas capazes de prevenir e/ou travar a neurodegeneração. Neste contexto, a utilização de probióticos, prebióticos, polifenóis e outros componentes da dieta capazes de modular o microbiota intestinal poderão vir a constituir importantes estratégias terapêuticas no contexto da DP.No presente documento, serão abordados vários mecanismos moleculares considerados relevantes na degeneração e morte dos neurónios dopaminérgicos que ocorre na DP. Será também discutido o papel do eixo microbiota-intestino-cérebro no desenvolvimento de tais mecanismos, bem como a potencial utilização de terapias inovadoras baseadas na modulação do microbiota.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta,accompanied by synucleinopathy.Several studies suggest that mitochondrial dysfunction, oxidative stress,neuroinflammation and α-synuclein play an important role in neurodegeneration.However, what triggers such mechanisms and makes neurodegeneration progressive and uncontrolled remains largely unclear. In this context, recently, several evidences strongly suggest that PD may start in the intestine and that the intestinal microbiota, an important modulator of the complex bidirectional communication that occurs between the brain and the gastrointestinal system (microbiota-gut-brain axis), may play a key role in the pathogenesis of this neurodegenerative disease.Since the etiology of PD remains unclear, this disease has no cure, and it is essential to develop new therapeutic strategies capable of preventing and/or stop the neurodegeneration.In this context, the use of probiotics, prebiotics, polyphenols, and other dietary components able of modulating the intestinal microbiota may become important therapeutic strategies in the context of neurodegenerative diseases.In this document, several molecular mechanisms underlying the degeneration and death of dopaminergic neurons that occur in PD will be discussed. The role of the microbiota-gut brain axis in the development of these mechanisms of neurodegeneration as well as the potential use of therapies based on the modulation of microbiota will also be discussed.
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Ribeiro, Andreia. « Probióticos e efeitos terapêuticos em patologias do sistema nervoso central ». Master's thesis, 2021. http://hdl.handle.net/10284/10462.
Texte intégralRésumé :
O trato gastrointestinal de um indivíduo saudável está colonizado por uma grande variedade e quantidade de microrganismos que compõem o microbiota intestinal, o qual desempenha um importante papel nos processos metabólicos, nutricionais, fisiológicos e imunológicos. Em situações de disbiose, resultante de desequilíbrios na composição ou função das espécies constituintes do microbiota, ocorrem alterações da função imunológica o que aumenta a suscetibilidade de desenvolver alergias, alterações metabólicas, doenças inflamatórias e doenças neurodegenerativas.
Os probióticos são suplementos alimentares contendo microrganismos vivos que, quando administrados em quantidades razoáveis, serão benéficos à saúde do seu consumidor ou hospedeiro. A sua administração exógena permite colonizar e estabilizar a composição da microflora, restabelecendo a sua função fisiológica vital, após desequilíbrios provocados pelo estilo de vida moderno e pelas várias doenças a ele associadas. Os
metabolitos produzidos por microrganismos probióticos através de diferentes mecanismos de ação, desempenham um importante papel na modulação imunológica e na manutenção da homeostase do microbiota.
O Eixo Microbiota-Intestino-Cérebro foi recentemente identificado com a descoberta de diversas vias hormonais e bioquímicas interligadas que relacionam o trato gastrointestinal e o cérebro. Este eixo desempenha um papel importante na regulação da saúde do hospedeiro, permitindo a comunicação bidirecional entre intestino e cérebro, o que sugere que o uso de probióticos poderá ter um forte potencial terapêutico no tratamento de doenças do sistema nervoso central como a Esclerose Múltipla, a Doença de Parkinson e a Doença de Alzheimer.The gastrointestinal tract of a healthy individual is colonized by a wide variety and quantity of microorganisms that make up the intestinal microbiota, playing an important role in metabolic, nutritional, physiological and immunological processes. In situations of dysbiosis, resulting from imbalances in the composition or function of the species that make up the microbiota, immune function may be compromized, increasing the susceptibility of developing allergies, metabolic changes, inflammatory diseases and neurodegenerative diseases. Probiotics are food supplements containing live microorganisms that, when administered in reasonable amounts, will be beneficial to the health of their consumer or host. Its exogenous administration allows colonization and stabilization of the microflora composition, restoring its vital physiological function, after imbalance due to modern lifestyle and associated diseases. Probiotic metabolites, through diverse mechanisms of action, play an important role in immunological modulation and maintenance of microbiota homeostasis. The Microbiota-Gut-Brain Axis was recently identified with the discovery of several interconnected hormonal and biochemical pathways linking the gastrointestinal tract and the brain. This Axis plays an important role in the regulation of host health by allowing bidirectional communication between the intestine and the brain, thus suggesting probiotic use as a promising therapeutic strategy for the treatment of central nervous system diseases such as multiple sclerosis, Parkinson's disease and Alzheimer's disease.
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Borrelli, Luca. « THE MICROBIOTA-GUT-BRAIN AXIS. A STUDY IN ZEBRAFISH (DANIO RERIO) ». Tesi di dottorato, 2015. http://www.fedoa.unina.it/10221/1/Borrell_Luca.pdf.
Texte intégralRésumé :
The microbiota is essential in the host's physiology, development, reproduction, immune system, nutrient metabolism, in brain chemistry and behavior. The gut microbiota plays a crucial role in the bidirectional gut–brain axis, a communication that integrates the gut and central nervous system (CNS) activities, and thus, the concept of microbiota–gut–brain axis is emerging where the microbes have considered as signaling components in the gut-brain axis. Animal studies reveals, in particular, that gut bacteria influence the brain-derived neurotrophic factor (BDNF) levels, and behavior specially after probiotic administration. How this alterations in brain chemistry are related to specific behavioral changes is unclear but it will likely be a focus of future research efforts. Among these animal studies, to our knowledge, no studies on the microbiota–gut–brain axis in zebrafish (Danio rerio) have been carried out. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's behavior and neurochemical gene expression. The purpose of this study was to determine whether probiotic strain can modulate gut commensal bacteria influencing brain neurochemistry and behavior in zebrafish. Thus, we treated adult zebrafish for 28 days with Lactobacillus rhamnosus, a probiotic strain which is one of the main components of the commensal microflora of human intestinal tract and it is widely used as a probiotic in mammals to adult male and female AB wild tipe zebrafish. We established differences between treated with probiotic strain and control group in shoaling behavior pattern, using a Video Tracker software; we quantified brain-derived neurotrophic factor (BDNF) gene expression by using RT-qPCR; we at last analyzed the microbiota profiles within two experimental groups by sing the culture-independent methods such as Denaturing Gradient Gel Electrophoresis (DGGE) and Next-Generation Sequencing (NGS). The probiotic treated group, compared to the control group, showed a statistically significant near two-fold increase in BDNF gene expression, different shoaling behavioural pattern and a shift in microbiota composition with a significant increase of Firmicutes and a reduction of Proteobacteria.
The results of each approach may support the existence of a microbiota–gut–brain axis, in adult zebrafish and in line with numerous animal studies we can speculate that microbiota manipulation could influence behavior and brain expression of BDNF.
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Barros, João Tomás da Silva. « Changes in the Gut-Brain axis during aging ». Master's thesis, 2020. http://hdl.handle.net/10316/93972.
Texte intégralRésumé :
Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaAtualmente, pensa-se que inflamação sub-crónica e um microbioma intestinal alterado poderão estar subjacentes à patogénese de doenças neurodegenerativas, tais como na doença de Parkinson. O descrito aumento do número de citocinas pró-inflamatórias tanto no sangue, como em biópsias colónicas de doentes de Parkinson permitiu conectar, assim, imunidade gastrointestinal com inflamação. Uma vez que os pacientes desta doença muitas vezes apresentam disfunção intestinal acrescenta peso à importância da interação intestino-cérebro no desenvolvimento da neurodegeneração. Uma vez que perturbações gastrointestinais podem ocorrer até décadas antes do aparecimento de sintomas motores, mudanças no microbioma intestinal poderão ser identificadas como prognóstico antecipado. Assim, a disrupção entre bactérias comensais e patogénicas no intestino, tal como acontece com o envelhecimento, poderá aumentar a suscetibilidade à doença de Parkinson.Este estudo teve como objetivo verificar que as alterações que ocorrem no microbioma com o envelhecimento, deixam ratinhos mais suscetíveis ao desenvolvimento da doença de Parkinson. Mais, ponderamos que a acumulação de ferro no intestino durante o envelhecimento fosse a causa deste desequilíbrio, um processo que poderia ser reversível com terapia de quelantes de ferro, revertendo assim a inflamação intestinal. Este estudo procurou ainda descobrir se uma redução de ferro no intestino seria suficiente para reduzir a neuroinflamação mediada pelas interações intestino-cérebro, e, como tal, a severidade da doença de Parkinson em ratinhos.Ratinhos C57BL/6 foram usados como modelo pré-clínico de modo a alcançar os objetivos deste estudo. Comparações entre ratinhos relativamente novos (8-12 semanas) e velhos (52-60 semanas) foram realizadas de forma a analisar a inflamação intestinal e a acumulação de ferro, com ou sem a administração de terapias quelantes. As interações intestino-cérebro foram avaliadas associando os resultados obtidos no intestino com um aumento na neuroinflamação e acumulação de ferro no cérebro. Um modelo farmacológico da doença de Parkinson foi induzido através da administração de 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), uma neurotoxina exclusiva dos neurónios dopaminérgicos da substantia nigra cérebro. Transplantes fecais também foram efetuados para avaliar se a alteração do microbioma intestinal influencia o perfil neuro inflamatório de ratos velhos e, consequentemente, a severidade da doença.Dados preliminares a suportar a hipótese colocada já foram adquiridos pelo mesmo laboratorio, tendo sido crucial a sua validação com o plano experimental proposto. Esta tese almejou conseguir provar que as mudanças no microbioma com o envelhecimento são capazes de influenciar o fenótipo neuro-inflamatório de ratinhos velhos, aumentando a sua suscetibilidade à doença. Esperou-se também mostrar que os mecanismos moleculares subjacentes a este fenómeno, necessitavam de acumulação de ferro no intestino, um processo que aumenta a patogenicidade bacteriana e modula a resposta imune.
Low-grade chronic inflammation and altered composition of gut microbiota have been suggested to underlie the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). An increased level of pro-inflammatory cytokines was found in both peripheral blood and colonic biopsies of PD patients, an observation that allowed linking gut immunity and inflammation. The notion that PD patients usually present intestinal dysfunction and constipation further strengthens the importance of a gut-brain interaction during the development of neurodegenerative diseases, like PD. Since gastro-intestinal (GI) manifestations often occur a decade before the appearance of severe motor deficits, changes in gut microbes can be identified as early PD symptoms. Hence, the disruption between commensal and pathogenic bacteria in the gut, as physiologically occurs during aging, is thought to favor an increased susceptibility to PD.This study aimed to verify that changes occurring in the gut microbiota during aging rendered mice more susceptible to PD. Moreover, we hypothesized that the accumulation of iron in the gut during aging was the underlying cause of this unbalance, a process that could be reversed with the administration of iron chelators that prevent these changes to trigger gut inflammation. This study was also able to assess whether a reduction of iron in the gut was capable to reduce the gut-brain axis-induced neuroinflammation and, as such, the severity of PD, in mice.C57BL/6 mice were used, as a pre-clinical animal model, to address the objectives of this study. Comparisons between relatively young (8-12-weeks old) and old (52-60-weeks old) mice was carried out, in terms of gut inflammation and iron accumulation, with or without the administration of iron chelation therapy. The gut-brain axis was evaluated by associating the results obtained in the gut with an increased neuroinflammation and iron accumulation in the brain. A pharmacological model of PD was induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin known to target exclusively dopaminergic neurons in the substantia nigra of the brain. Fecal transplantation was also used to address whether changing the composition of the gut microbiota could influence the neuro-inflammatory profile of aged mice and, subsequently, the severity of PD.Preliminary data supporting the hypotheses put forth were already obtained in the laboratory, so it was crucial their validation with the experimental plan proposed to complete my studies. This research was expected to prove that changes in gut microbiota occurring during aging were capable to influence the neuro-inflammatory phenotype of older mice and to increase the severity of PD. Furthermore, it was also expected to show that the molecular mechanism underlying this phenomenon relied on the accumulation of iron in the gut, a process known to increase bacteria pathogenicity and to modulate the inflammatory response. Lastly this study also addressed the salutary effect of iron chelation therapy in PD, providing proof of concept that its beneficial effects were also due to its ability to diminish gut inflammation.
Outro - Investigator Programme (IF/01495/2015). Financiamento concedido pela Fundação pela Ciência e Tecnologia (FCT) para o projeto de investigação científica titulado: “Immunity and inflammation in Parkinson’s disease”.
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Ficara, Austin Charles. « Influence of the human gut microbiota on depression and anxiety ». Thesis, 2019. https://hdl.handle.net/2144/38603.
Texte intégralRésumé :
Depression and anxiety disorders affect upwards of one in six individuals at some point in their life making them the most prevalent mental illnesses today. Recent evidence has suggested a possible correlation between the human gut microbiota and the development of depressive and anxiety-like symptoms through a signaling pathway termed the microbiota-gut-brain axis. In both animals and individuals suffering from depression and anxiety-like symptoms, alterations in their gut microbial composition seem to compromise the function of this pathway. In addition to this microbiota-gut-brain axis, other microbiota-derived molecules have been linked to symptoms of depression and anxiety. Given this emerging role of the gut microbiome and gut–brain axis, it is crucial to understand the factors shaping our gut microbiome in order to determine potential therapeutic strategies to treat depression and anxiety. Following a concise review of the human microbiome, depression/anxiety, and the gut-brain axis, I will examine the gut microbiota role as a regulator of depression and anxiety. In addition, other biological markers associated with both the gut microbiome and these disorders will be reviewed. Lastly, I will evaluate the gut microbiome as a prospective therapeutic target for mental illnesses such as depression and anxiety.
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Kosenkova, Inna. « Possible impact of the gut microbiota on the excitability of the brain ». Doctoral thesis, 2018. http://hdl.handle.net/11562/978978.
Texte intégralRésumé :
It is becoming increasingly evident that the role of the gut microbiota (GM) is not limited by the walls of the gastrointestinal tract (supporting the digestion, absorption of nutrients, intestinal motility and resistance to pathogens), but it also influences normal physiology of the whole organism and contribute to the broad range of diseases including those affecting the central nervous system (CNS). The growing appreciation of the role of intestinal bacteria in brain physiology has led to the establishment of so called “gut-brain axis”, or the “microbiota-gut-brain axis”, a bidirectional communication network between the gut and the brain. We hypothesized that gut microbiota form subjects affected by neural pathology can modulate in healthy subjects excitability in CNS and, finally, positively correlate with the level of seizure activity. The data obtained in this study suggests that mice received “pro-pathological” microbiota have compromised brain excitability. Microbiota composition of the donors with induced temporal lobe epilepsy (TLE) was characterized by the increase in Sutterella, Prevotella, Dorea, Coprobacillus and Candidatus Arthromitus in comparison with the baseline. These alterations, through the GBA, may possibly have an effect on the excitability of the brain and subsequently on the threshold for the seizure activity.
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Chaung, Chung-Wei, et 莊仲薇. « Effects of Lactobacillus reuteri YM0570 and commercial multiple strain probiotics product on microbiota-gut-brain axis in antibiotics-induced dysbiosis mice model ». Thesis, 2019. http://ndltd.ncl.edu.tw/handle/qzp4jk.
Texte intégral
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Prosperi, Margherita. « In-depth Understanding of Gastrointestinal (GI) Problems in Autism Spectrum Disorder (ASD) : Nature, Expression, and Possible Therapeutic Approaches ». Doctoral thesis, 2022. http://hdl.handle.net/2158/1265034.
Texte intégralRésumé :
Autism Spectrum Disorder (ASD) is a relatively frequent disorder with a high longitudinal diagnostic stability (Prosperi 2010), characterized by a significant individual, familial, and societal burden (Horlin et al. 2014). Gastrointestinal (GI) problems are more frequent in children with ASD than in typically developing (TD) peers (Prosperi 2016) and are associated with low functioning and high psychiatric symptoms (Prosperi et al. 2017).
This dissertation offers a possible analysis and interpretation of GI symptoms through a psychiatric perspective based on various clinical and biochemical investigations.
The first part is an overview with an introductory critical analysis of the literature and a description of the findings emerging from the specific research I have dealt with, all investigating GI problems in children with ASD. Studies concerning the microbiota-gut-brain axis with their therapeutical implications, the results of a survey concerning eating habits and the findings of a prevalence study on celiac disease are summarized.
The second part concerns a randomized controlled study on the role of probiotics on clinical and biochemical parameters funded by the Italian Ministry of Health concerning a sample of preschoolers with ASD (Santocchi et al. 2016). The results were presented by chapters, partitioning the sample into subgroups based on the data available for each experimental question.
As shown below, children with ASD and GI symptoms exhibit their disturbances with different behaviors than TD children, have a particular intestinal microbiota and fecal metabolome than children with ASD without GI symptoms, and the nature of their disturb is more likely functional than organic. Promising results emerge from a clinical trial with probiotics on GI symptoms and behavioral features for children with ASD.
Future experimental trials considering TD control samples will provide a baseline and significantly empower the robustness of some of these promising findings.
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Ferreira, Ana Carolina Barros Bemhaja. « Disfunção da Barreira Hematoencefálica na Esclerose Múltipla : a chave do problema ou da solução ? » Master's thesis, 2018. http://hdl.handle.net/10316/84372.
Texte intégralRésumé :
Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaA Esclerose Múltipla (EM) é uma doença autoimune com elevada incidência a nívelglobal, que atinge em maior escala indivíduos do sexo feminino. Pensa-se que a sua etiologia assenta numa complexa associação de diversos fatores ambientais com determinadas características genéticas preexistentes. Esta doença está associada a uma desregulação do sistema imunitário e afeta o sistema nervoso central (SNC), causando desmielinização e degradação axonal. Assim, a EM assume um caráter neurodegenerativo e neuroinflamatório, com consequências a nível físico, cognitivo e emocional. Este descontrolo da resposta imunitária é considerado o principal responsável pela fisiopatologia da EM, pelo que as armas terapêuticas existentes para modificar o curso da doença se baseiam, fundamentalmente, em mecanismos de imunomodulação. Contudo, a barreira hematoencefálica (BHE) também parece exercer um papel essencial nos processos fisiopatológicos da doença, uma vez que a sua estrutura se encontra comprometida, impedindo o correto desempenho da sua função protetora do SNC. Por outro lado, verifica-se a existência de uma interação bidirecional entre a microbiota intestinal e a BHE, o que influencia a sua estabilidade e integridade.Neste sentido, é importante esclarecer a correlação desta barreira e do ambiente entérico com o desenvolvimento de EM, de modo a poder conceber estratégias farmacológicas promissoras com mecanismos de ação inovadores, capazes de revolucionar o mercado terapêutico desta doença, melhorando a sua evolução, a qualidade de vida e o bem-estar dos doentes.
Multiple sclerosis (MS) is an autoimmune disease with a high global incidence, which impacts female individuals on a larger scale. It is thought that its etiology is based on a complex association of several environmental factors with preexisting genetic features. This disease is associated to an immune system dysregulation and affects the central nervous system (CNS), causing demyelination and axonal damage. Therefore, MS assumes a neurodegenerative and neuroinflammatory character, with physical, cognitive and emotional consequences. This dysregulation of the immune response is considered the main factor responsible for MS pathophysiology, so the existing therapeutic weapons to modify the disease course are mainly based on immunomodulation mechanisms. Nevertheless, the blood-brain barrier (BBB) seems to play an essential role in the pathophysiological processes of the disease, since its structure is compromised, hampering the correct performance of its protective function of the CNS. On the other hand, there is a bidirectional interaction between the gut microbiota and the BBB, which influences its stability and integrity. Thus, it is important to clarify the correlation of this barrier and the enteric environment with the development of MS, so that it is possible to design promising pharmacological strategies with innovative mechanisms of action, capable of revolutionizing the therapeutic market of this disease in order to improve its evolution, patients’ quality of life and well-being.
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Ganci, Michael. « Has Psychology Ignored Our Gut Feelings ? Exploring the Relationship Between Gut Microbiota and Psychological Symptoms : A Call for a Paradigm Shift ». Thesis, 2021. https://vuir.vu.edu.au/43572/.
Texte intégralRésumé :
The profession of psychology has long been entrenched in a traditional central nervous system (CNS) centric framework. This specialisation has had its benefits and contributed to current knowledge of psychological symptoms and disorders. However, this reductionist approach has led to gaps in knowledge that will continue to persist without a broader appreciation of the complexity of the human body. Broader consideration of bodily systems may provide greater insight into the aetiology, diagnosis, treatment, and prevention of psychological symptoms and disorders.
The enteric nervous system (ENS) and its resident gut microbiota (GM) has emerged as a peripheral influence on psychological functioning. The GM refers to the trillions of microorganisms residing in the gut including, but not limited to, bacteria, fungi, and protozoa. The GM has coevolved with its human hosts to share a highly complex multidirectional relationship. In a state of symbiosis, GM play a key role in protecting against pathogen colonisation, strengthening and maintaining the epithelial barrier, and nutrient absorption through metabolism, therefore promoting host health. On the other hand, in a state of dysbiosis (imbalances in the composition of GM), this mutually beneficial relationship between host and GM shifts towards a more antagonistic one. Dysbiosis of GM, as well as specific gut microbes themselves, have been associated with a wide range of psychological symptoms and disorders. To date, of the organisms that reside within the GM, bacteria have received the majority of attention in brain-gut-microbiota axis (BGMA) research.
This thesis broadly aims to position the BGMA as falling within the purview of psychologists, while also exploring the concept of the microgenderome in a series of three papers. Paper 1 is a review paper which aimed to demonstrate that GM are intrinsically linked with each stage of psychological disorder, from aetiology through to treatment and prevention. The paper was framed around the Four P model of case formulation, often used in psychological practice.
With the neglect of focus on other microorganisms, paper 2 was the first to investigate the effect of these protozoa on psychological symptom severity. Specifically, Paper 2 presents the results of a cross-sectional, retrospective study of the differences in Depressive, Neurocognitive, Stress and Anxiety, and Sleep and Fatigue symptom severity between individuals negative for intestinal protozoa (n= 563) compared to those positive for common protozoa Blastocystis sp. (n= 274), Dientamoeba fragilis (n= 69), or both (n= 73). The findings demonstrated that there was no statistically significant effect of either protozoan, or co-carriage, on psychological symptom severity for either males or females. Utilising correlational analyses, a retrospective cross-sectional exploration of the association between GM and Depressive, Neurocognitive, Stress and Anxiety, and Sleep and Fatigue symptom severity was carried out in Paper 3. While the overall sample was made up of 4610 clinically diverse participants, sample size for each correlational analysis was dependent on available data. The pattern of associations between several GM species and psychological symptom severity were distinctly different between males and females, providing support for the microgenderome. The results demonstrated that some bacterial species found in common probiotic supplements were positively correlated with symptom severity. The results provide support for the notion that, in future, modulation of GM may be appropriate as an ancillary treatment of psychological symptoms, however further research is needed before their implementation in treatment plans.
Collectively, this thesis demonstrates that expanding the CNS-centric approach to include peripheral systems may revolutionise the way that psychological illness, and its prevention and treatment are conceptualised. Future directions for research and clinical practice are discussed which include methodological and practical challenges that must be overcome to substantiate the need for a paradigm shift for the discipline of psychology.
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Ambrožová, Lucie. « Střevní mikrobiota a poruchy nálady ». Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-347667.
Texte intégralRésumé :
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Lucie Ambrožová Supervisor: Doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: Intestinal microbiota and mood disorders The intestinal microbiom is composed mainly of two dominated strains - Bacteroidetes and Firmicutes. The other strains are just not numerous like the previous ones. The specimens have the invariable core of microbiom which doesn't change in time. Nevertheless they have also the transient gut bacteria, which change during their life. Intestinal microbiom is influenced by many factors. Between them we can categorize for example the way of the childbirth, the breast - feeding, the alimentation, the state of health, and the medicaments. Every specimen has own specific microbiom. It was found that human population is possible to divide into three intestinal groups or enterotypes. To each enterotype dominates different bacterial strain. It was proved that intestinal microbiom communicates with the brain and it works also vice versa. This communication system is called "brain - intestine" and takes several ways in several body systems (such as nervous, endocrine, metabolic, and immune). To normal development of the brain is needed the right colonisation of non...
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Ceppa, Florencia Andrea. « Diet:microbiota interaction in the gut focus on amino acid metabolism ». Doctoral thesis, 2016. http://hdl.handle.net/10449/33118.
Texte intégralRésumé :
This study aims to measure the impact of protein and amino acid fermentation
on the composition and metabolic output of gut microbiota. Although dissimilatory
pathways have been described for most amino acids, microbial degradation
routes within the gut microbiota are relatively unexplored. The objectives were (1)
to characterize amino acid breakdown by the colonic microbiota, (2) to determine
the fermentation products formed from individual amino acids/protein (3) to examine
how amino acid metabolism is impacted by the presence of a fermentable fiber
(prebiotic inulin) and finally (4) to evaluate with an in vivo model (trout fish) diet:-
microbe interactions and the development of gut microbiota during fish farming.
Interactions between the healthy human intestinal microbiota of the distal colon
and different combinations of nutrients were simulated using in vitro pH-controlled
anaerobic batch cultures of human faeces. Combining high-throughput sequencing
of 16S rRNA amplicons, with high-throughput 1
H NMR, changes in faecal
microbiota composition and metabolic output were measured. During exogenous
substrate microbial fermentation (e.g. beef, Trp or fish feed) in the large bowel
bioactive compounds (harmful or beneficial) are produced. Many factors affect the
gut-microbial metabolism including pH, type and quantity of growth substrate (e.g.
protein/carbohydrate) and make up of the gut microbiota. Considerable interindividual
variation was observed in response to different digested substrates but over
all, the beneficial impact of prebiotic fiber fermentation on production of bioactive
compounds from amino acids/proteins was confirmed in this study. In trout, although
our dietary intervention with essential oils had little impact on the gut microbiota,
the study showed for the first time a dramatic shift in the composition and diversity
of the gut microbiota in juvenile compared to adult fish. These observations may
have relevance in designing dietary strategies to reduce chronic diseases like colon
cancer and heart disease and for fish farming respectively