Literatura académica sobre el tema "Microbiota, gut-brain axis, epilepsy, inflammation"

Several studies point to a vital role for gut microbiota (GM) in preventing disease and reducing inflammation in humans. Gut microbiota has an important relationship with the human brain-gut axis, and the biological metabolites they produce are closely linked to the function of nervous system. Ketogenic diet (KD) is thought to be effective on the makeup of GM and thus affecting human health due to its low calorie and fiber consumption. Recent research has found KD can affect GM composition under pathological conditions, such as drug refractory epilepsy (DRE). So as to achieve the purpose of treating DRE. Therefore, this article aims to explore the effect of KD on the human GM and explore whether it has important implications for human health. Finally, we found that KD can modulate human health by affecting gut microbiota richness, increasing some microbes that can produce beneficial metabolites, and reducing some pro-inflammatory microbes to prevent and treat specific diseases.

The purpose of the review was to study the effects of stress on the gut microbiota. Results and discussion. The gut microbiota forms a complex microbial community that has a significant impact on human health. The composition of the microbiota varies from person to person, and it changes throughout life. It is known that the microbiome can be altered due to diet, various processes, such as inflammation and/or stress. Like all other areas of medicine, microbiology is constantly growing. The gut microbiota lives in a symbiotic relationship with the human host. It is now believed to interact with almost all human organs, including the central nervous system, in the so-called «gut-brain-microbiome axis». Recently, a growing level of research is showing that microbes play a much bigger role in our lives than previously thought, and can have a myriad of effects on how we behave and think, and even on our mental health. The relationship between the brain and the microbiota is bidirectional and includes endocrine, neuronal, immune, and metabolic pathways. The microbiota interacts with the brain through various mechanisms and mediators, including cytokines, short-chain fatty acids, hormones, and neurotransmitters. According to the hypothalamic-pituitary-adrenocortical axis imbalance theory, hormonal imbalances are closely related to psychiatric illness, anxiety, and stress disorders. Therefore, the gut microbiome is closely related to the development and functioning of this axis. The microbiota can influence neurotransmitter levels in a variety of ways, including the secretion of gamma-aminobutyric acid, norepinephrine, dopamine, and serotonin, and can even regulate serotonin synthesis. These neurotransmitters can influence the hormonal status of the body, and the hormones themselves can influence the formation of the qualitative and quantitative composition of the microbiota. Accordingly, a change in the composition of the intestinal microbiota may be responsible for modifying the hormonal levels of the human body. The endocrine environment in the gut can also be modulated through the neuro-enteroendocrine system. Conclusion. Today, it is known that microbiota changes can be associated with several disorders of the nervous system, such as neuropsychiatric, neurodegenerative and neuroinflammatory processes. Research in recent decades has shown that disorders of the nervous system and mood disorders are associated with changes in the balance of neurotransmitters in the brain. Therefore, understanding the role of microbiota in the development and functioning of the brain is of great importance

The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.

Canine idiopathic epilepsy is a common neurological disease characterized by the enduring predisposition of the cerebral cortex to generate seizures. An etiological explanation has not been fully identified in humans and dogs, and, among the presumed causes, several studies support the possible involvement of gut microbiota. In this review, the authors summarize the evidence of the reasonable role of gut microbiota in epilepsy through the so-called gut–brain axis. The authors provide an overview of recent clinical and preclinical studies in humans and dogs in which the modulation of intestinal permeability, the alteration of local immune response, and the alteration in production of essential metabolites and neurotransmitters associated with dysbiosis could be responsible for the pathogenesis of canine epilepsy. A systematic review of the literature, following the PRISMA guidelines, was performed in two databases (PubMed and Web of Science). Eleven studies were included and reviewed supporting the connection between gut microbiota and epilepsy via the gut–brain axis.

Over unimaginable expanses of evolutionary time, our gut microbiota have co-evolved with us, creating a symbiotic relationship in which each is utterly dependent upon the other. Far from confined to the recesses of the alimentary tract, our gut microbiota engage in complex and bi-directional communication with their host, which have far-reaching implications for overall health, wellbeing and normal physiological functioning. Amongst such communication streams, the microbiota–gut–brain axis predominates. Numerous complex mechanisms involve direct effects of the microbiota, or indirect effects through the release and absorption of the metabolic by-products of the gut microbiota. Proposed mechanisms implicate mitochondrial function, the hypothalamus–pituitary–adrenal axis, and autonomic, neuro-humeral, entero-endocrine and immunomodulatory pathways. Furthermore, dietary composition influences the relative abundance of gut microbiota species. Recent human-based data reveal that dietary effects on the gut microbiota can occur rapidly, and that our gut microbiota reflect our diet at any given time, although much inter-individual variation pertains. Although most studies on the effects of dietary macronutrients on the gut microbiota report on associations with relative changes in the abundance of particular species of bacteria, in broad terms, our modern-day animal-based Westernized diets are relatively high in fats and proteins and impoverished in fibres. This creates a perfect storm within the gut in which dysbiosis promotes localized inflammation, enhanced gut wall permeability, increased production of lipopolysaccharides, chronic endotoxemia and a resultant low-grade systemic inflammatory milieu, a harbinger of metabolic dysfunction and many modern-day chronic illnesses. Research should further focus on the colony effects of the gut microbiota on health and wellbeing, and dysbiotic effects on pathogenic pathways. Finally, we should revise our view of the gut microbiota from that of a seething mass of microbes to one of organ-status, on which our health and wellbeing utterly depends. Future guidelines on lifestyle strategies for wellbeing should integrate advice on the optimal establishment and maintenance of a healthy gut microbiota through dietary and other means. Although we are what we eat, perhaps more importantly, we are what our gut microbiota thrive on and they thrive on what we eat.

Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota–brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.

Epilepsy is a non-communicable brain disorder characterized by an individual's proclivity for spontaneous epileptic seizures. Epilepsy may be classified into six types: genetic, structural, metabolic, infectious, immune-related, and unexplained causes. Numerous current findings have shown evidence that an imbalance in the gut microbiota is a cause of epilepsy. Between the gut microbiota and the brain systems, there are five putative communication pathways. The neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis, intestinal bacteria's production of neurotransmitters, the intestinal immune system, and the relationship between the intestinal mucosal barrier and the blood-brain barrier are among them. Future epilepsy interventions might include modifications of antiepileptic medications, a ketogenic diet, and probiotics as a possible treatment in the gut flora. However, further research is required to assess long-term therapeutic benefits.

Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut–liver–brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut–liver–brain axis.

Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).

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.

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.

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.

Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e Tecnologia
Atualmente, 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”.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
A 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.

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.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
A 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.

Over the past decade, a growing body of evidence has validated the essential role of the gut microbiome in regulating diverse physiologic processes, spanning gut-related disease to neural function. While many factors are involved, diet is the primary driver of global microbial composition and function. Studies from animal models and humans suggest that the ketogenic diet can reshape the gut microbiome. However, the relevance of the altered microbiota is still under investigation. Since the gut microbiome is implicated in modulating brain function via metabolic, immunologic, and endocrine pathways, a possible role of the microbiota–gut–brain axis in mediating the neural response to the ketogenic diet has been proposed. This chapter outlines how the ketogenic diet affects the gut microbiota and the implications of such ketogenic diet-induced phenotypes. Special attention is paid to interactions between the diet, gut microbiota, and neurodevelopmental disorders, including epilepsy and autism spectrum disorder.

The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer’s disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.

Vascular cognitive impairment (VCI), the second most common cause of dementia in elderly people, is a term that refers to all forms of cognitive disorders that can be attributed to cerebrovascular disease such as manifestations of discrete infarctions, brain hemorrhages, and white matter lesions. The gut microbiota (GM) has emerged recently as an essential player in the development of VCI. The GM may affect the brain’s physiological, behavioral, and cognitive functions through the brain-gut axis via neural, immune, endocrine, and metabolic pathways. Therefore, microbiota dysbiosis may mediate or affect atherosclerosis, cerebrovascular disease, and endothelial dysfunction, which are the predominant risk factors for VCI. Moreover, the composition of the GM includes the bacterial component lipopolysaccharides and their metabolic products including trimethylamine-N-oxide and short-chain fatty acids. These products may increase the permeability of the intestinal epithelium, leading to systemic immune responses, low-grade inflammation, and altered signaling pathways that are associated with the pathogenesis of VCI. In this review, we discuss the proposed mechanisms of the GM in the maintenance of VCI and how it is implicated in acquired metabolic diseases, particularly in VCI regulation.

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is accompanied by cognitive impairment and shows representative pathological features, including senile plaques and neurofibrillary tangles in the brain. Recent evidence suggests that several systemic changes outside the brain are associated with AD and may contribute to its pathogenesis. Among the factors that induce systemic changes in AD, the gut microbiota is increasingly drawing attention. Modulation of gut microbiome, along with continuous attempts to remove pathogenic proteins directly from the brain, is a viable strategy to cure AD. Seeking a holistic understanding of the pathways throughout the body that can affect the pathogenesis, rather than regarding AD solely as a brain disease, may be key to successful therapy. In this review, we focus on the role of the gut microbiota in causing systemic manifestations of AD. The review integrates recently emerging concepts and provides potential mechanisms about the involvement of the gut-brain axis in AD, ranging from gut permeability and inflammation to bacterial translocation and cross-seeding.

Given the complex bidirectional communication system that exists between the gut microbiome and the brain, there is growing interest in the gut microbiome as a novel and potentially modifiable risk factor for Alzheimer’s disease (AD). Gut dysbiosis has been implicated in the pathogenesis and progression of AD by initiating and prolonging neuroinflammatory processes. The metabolites of gut microbiota appear to be critical in the mechanism of the gut-brain axis. Gut microbiota metabolites, such as trimethylamine-n-oxide, lipopolysaccharide, and short chain fatty acids, are suggested to mediate systemic inflammation and intracerebral amyloidosis via endothelial dysfunction. Emerging data suggest that the fungal microbiota (mycobiome) may also influence AD pathology. Importantly, 60% of variation in the gut microbiome is attributable to diet, therefore modulating the gut microbiome through dietary means could be an effective approach to reduce AD risk. Given that people do not eat isolated nutrients and instead consume a diverse range of foods and combinations of nutrients that are likely to be interactive, studying the effects of whole diets provides the opportunity to account for the interactions between different nutrients. Thus, dietary patterns may be more predictive of a real-life effect on gut microbiome and AD risk than foods or nutrients in isolation. Accumulating evidence from experimental and animal studies also show potential effects of gut microbiome on AD pathogenesis. However, data from human dietary interventions are lacking. Well-designed intervention studies are needed in diverse populations to determine the influence of diet on gut microbiome and inform the development of effective dietary strategies for prevention of AD.