Dissertationen zum Thema „Microbiome engineering“
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Nguyen, Le Thanh Tu. „Engineering the human gut microbiome through personalized dietary interventions“. Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/130187.
Der volle Inhalt der QuelleCataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
The human gastrointestinal tract is home to a dense and dynamic microbial community. The composition and metabolic output of the human gut microbiota have been implicated in many diseases: from inflammatory bowel disease, colorectal cancer, and diarrheal diseases to metabolic syndromes like diabetes. Treatment of these diseases will likely require targeted therapeutic interventions aimed at modulating the abundance and metabolism of specific commensal microbial species or probiotics. A promising avenue for such interventions is through diet, where the dietary components act as substrates for the species producing beneficial metabolites one wishes to enrich. In this thesis, I focus on a dietary intervention study in healthy individuals. Since the human gut microbiota is known for its highly heterogeneous composition across different individuals, it comes as no surprise that a more personalized approach is preeminent.
We first test effects of multiple micronutrients spiked into a fixed diet. Using a highly controlled diet within the cohort, we identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins. However, select macronutrient spike-ins like unsaturated or saturated fat and protein, produce no predictable response. We next investigate prebiotic supplement in diet further as well as its downstream products, short chain fatty acids, in the digestive tract. We look to alleviate the stress of a highly controlled, low complexity diet on participants by testing the effect of different prebiotics simultaneously ex vivo. We show that individuals vary in their microbial metabolic phenotypes (as in they produce different quantities and proportions of short chain fatty acids from the same prebiotic inputs) mirroring differences in their microbiota composition.
Finally, we run a pilot study to elucidate how closely our ex vivo experiment results may reflect the in vivo changes following a short-term dietary fiber supplementation. In addition to obtaining preliminary data on this direct comparison, we also explore different parameters for generating high-throughput data on personalized dietary interventions. Together, these projects provide the framework for building a predicative model for the effect that prebiotic dietary supplementation will have on gut microbiota's composition. Such a prediction model would be equally helpful in both enhancing individuals' gut health and improving gut dysbiosis in cases of disease.
by Le Thanh Tu Nguyen.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biological Engineering
Duvallet, Claire Marie Noëlle. „Mining the human microbiome for clinical insight“. Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/123061.
Der volle Inhalt der QuelleCataloged from PDF version of thesis.
Includes bibliographical references.
The human microbiome is essential for health and has been implicated in many diseases. DNA sequencing has enabled the detailed characterization of these human-associated microbial communities, leading to a rapid expansion in studies investigating the human microbiome. In this thesis, I describe multiple projects which overcome various data analysis challenges to extract useful clinical insights from microbiome data. In the first project, I present an analysis of lung, stomach, and oropharyngeal microbiomes. I leverage data collected from multiple sites per patient to identify aspiration-associated changes in the relationships between these communities, discovering new properties of the aerodigestive microbiome and suggesting new approaches for treatment. In the second project, I perform a meta-analysis of case-control gut microbiome datasets with standard data processing and analysis methods.
I find consistent patterns characterizing disease-associated microbiome changes and a set of shared associations which could inform clinical treatment and therapeutic development approaches for different microbiome-mediated diseases. Enabled by this work, in the third project I contribute to the development of a method to correct for batch effects in case-control microbiome studies. In the fourth project, I describe a framework for rational donor selection in fecal microbiota transplant clinical trials in which knowledge derived from clinical and basic science research is used to inform which donor is selected for fecal transplants, increasing the likelihood of successful trials. Finally, I present preliminary results analyzing the microbiome and metabolome of residential sewage as a novel platform for community-level public health surveillance.
Together, these projects demonstrate a variety of approaches to mine the human microbiome for clinically-relevant insights and suggests multiple avenues forward for translating findings from microbiome data analyses into clinical and public health impact.
by Claire Marie Noëlle Duvallet.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biological Engineering
Eain, Marc Mac Giolla, Joanna Baginska, Kacy Greenhalgh, Joëlle V. Fritz, Frederic Zenhausern und Paul Wilmes. „Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface“. ELSEVIER SCIENCE BV, 2017. http://hdl.handle.net/10150/623282.
Der volle Inhalt der QuelleHolcomb, Steven John. „An oxygen-controlled in vitro model of the gastrointestinal human-microbiome interface“. Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/115669.
Der volle Inhalt der QuelleCataloged from PDF version of thesis.
Includes bibliographical references (pages 86-88).
The gastrointestinal system plays a vital role in the functioning of the human body, processing food into useable energy, controlling homeostasis, and serving as the front line of the immune system. The intestines are aided in their many functions by the gut microbiome, a collection of 100 trillion anaerobic bacteria cells that live inside the GI tract. Although they play an essential part in the organ system, they remain little-represented in in vitro gastrointestinal models because of the difficulty of replicating the anaerobic conditions of the intestines. We constructed an in vitro model capable of growing aerobic epithelial intestinal cells along with anaerobic microbes in the same bioreactor. A device called the apical flow module seals a 12-well transwell and provides an inlet and outlet port into the apical chamber. Media is deoxygenated using nitrogen bubbles before it is pumped using a nitrogen-actuated pneumatic pump block. Microbes are injected into the anaerobic fluid through a rubber septum injection port before the fluid flows into the sealed transwell. Effluent is collected in sterile tubes at a controlled height so as to regulate the apical side pressure. Oxygen is provided to the basolateral human epithelial cells through basolateral circulation achieved using a pneumatic circulation plate. Preliminary testing confirms our ability to control the oxygen in all parts of the system and to grow cocultures of human and bacteria cells. Epithelial cells grown in our bioreactor show signs of behaving more similarly to cells in vivo when exposed to the conditions present in our system, providing researchers with an oxygen-controlled gastrointestinal in vitro model.
by Steven John Holcomb.
S.M.
Balhouse, Brittany Nicole. „N-(3-Oxododecanoyl)-L-Homoserine Lactone in the Breast Tumor Microenvironment“. Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/78027.
Der volle Inhalt der QuelleMaster of Science
Kearney, Sean M. (Sean Michael). „Towards engineering the gut microbiota“. Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/119909.
Der volle Inhalt der QuelleThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
The human gastrointestinal tract is home to a dense and dynamic microbial community. Recent advancements in sequencing technology have revealed numerous relationships between the composition of these communities and human and health and disease. In some cases, researchers have shown causal relationships between the presence or absence of particular microorganisms and disease. These findings offer promise for using microorganisms or microbial communities to modulate health and disease, but to date, we lack tools and mechanistic insight needed for rational engineering of these communities. Understanding how microorganisms enter, colonize, grow, and disperse to new hosts present key considerations for rational engineering of the human gastrointestinal tract. In this thesis, I use experimental studies of the human and murine gastrointestinal tract to address these considerations. In the first study, I examined endospores and other resistant cell types in the gastrointestinal communities of unrelated humans to identify the ecological role of these states in the distribution of bacterial populations in healthy people. I used this information to infer shared roles for these organisms in successional states in the human gut, and identify host- and diet-derived metabolites as environmental signals mediating the growth and colonization of these organisms. In the second study, I examined the potential for using targeted manipulations of diet to favor selective growth and colonization by an introduced bacterium in the murine gastrointestinal tract. I showed that resource exclusivity of this bacterium permits its selective expansion in this environment, and negatively impacts the growth of other commensals. Central to the goal of rational engineering of the gut microbiota, these studies reveal ecological considerations that may promote or inhibit colonization by introduced commensals in this complex ecosystem. This work invites provides a conceptual framework for integrating systems microbial ecology with engineering design to manipulate the composition of the gastrointestinal microbiota.
by Sean M. Kearney.
Ph. D.
Dijamentiuk, Alexis. „Propagation de communautés bactériennes : modelage, stabilisation et sélection pour la biopréservation“. Electronic Thesis or Diss., Université de Lorraine, 2023. http://www.theses.fr/2023LORR0124.
Der volle Inhalt der QuelleRecent discoveries about microbial communities, or microbiota, have revealed considerable biotechnological potential in a variety of fields. They are considered essential to accelerate innovation in food production systems. However, existing processes are not adapted to the cultivation of microbiota. One major barrier to community propagation is competition between microorganisms, which can lead to an undesirable reduction in biodiversity within the culture reactor. This phenomenon can lead to communities that lack the desired functionality. The objective of this thesis was to study the influence of microbiota propagation, under controlled conditions, on their structure and function. During this work, a process of microbial culture excluding microbial competition for the propagation of bacterial communities was developed. The chosen strategy is based on the micro-confinement and spatial segregation of bacteria within a broth structured as an invert emulsion. The effect of the invert emulsion culture on the growth of individual bacteria was studied, then the effect of this system on the dynamics of communities propagated according to a sequential regime, or backslopping, as well as that exerted by a conventional non-emulsified system was investigated. The results showed that the use of an inverse emulsion leads to the generation of new community structures during propagation, and that the use of the classical culture leads to their stabilization. The different behaviors of these two culture systems make them complementary tools for the modeling and the propagation of microbial communities. Finally, the effect of propagation on the functional variability of communities was studied in a biopreservation context. The screening of propagated raw milk microbiota showed that they differed in terms of robustness and reproducibility of anti-Listeria activity, emphasizing the need to take into account the functional variability of communities when selecting communities of interest for microbiota engineering
Krishnan, Smitha. „Gut Microbiota Metabolites Modulate Inflammation in Non- Alcoholic Fatty Liver Disease“. Thesis, Tufts University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10812893.
Der volle Inhalt der QuelleRecent findings, including our own work, demonstrated that intestinal microbiota species produce bioactive metabolites that engage host cellular pathways. Microbiota-derived metabolites have also been detected in circulation and in the, setting up the intriguing possibility that these bacterial products could directly interact with host cellular pathways at distant sites. The study described in this abstract investigates the hypothesis that gut microbiota dysbiosis perturbs the balance of immunomodulatory microbiota metabolites, which exacerbates liver inflammation in steatosis. We utilize a multi-omic approach to identify microbiota-dependent immunomodulatory metabolites and characterize their effects on liver inflammation and metabolic function. In summary, we show that the levels of AAA-derived microbiota metabolites are significantly depleted in a diet model of liver steatosis, and that these metabolite can act directly on hepatocytes to modulate inflammatory pathways. Our results also show that the microbiota metabolites are ligands for the AhR, which could provide a mechanistic link for the observed anti-inflammatory effects. Taken together, our findings support the hypothesis that dysbiosis of the gut microbiota could predispose the liver to inflammation in diet-induced steatosis through an altered microbiota metabolite profile. Prospectively, additional insights into the mechanisms underlying the link between microbiota dysbiosis and NAFLD could provide novel strategies to treat or prevent the progression of fatty liver diseases through the use of probiotics or postbiotics.
Blackburn, Matthew Christopher. „Development of new tools and applications for high-throughput sequencing of microbiomes in environmental or clinical samples“. Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/62136.
Der volle Inhalt der QuelleCataloged from PDF version of thesis.
Includes bibliographical references (p. 61-65).
Novel sequencing technologies are rapidly advancing studies of microbial community structure and diversity. Sequencing platforms like the Illumina Genome Analyzer II (GAI1) and the Applied Biosystems SOLiD enable experiments that were previously too expensive or time-consuming by providing a very large number of short reads at a significantly lower cost per base pair (bp) than conventional longer-read systems like the Roche-454 GS FLX pyrosequencing instrument. Short-read platforms, however, are not readily amenable to some applications like metagenomics and metatranscriptomics, and therefore pyrosequencing remains the dominant sequencing technique in these fields. The primary reason short-read technologies have not been used for metagenomic analyses is due to the difficulty of confidently assigning phylogeny or putative gene function to short sequences. In an effort to overcome this limitation, a strategy was developed for preparing libraries from sheared genomic DNA with tunable size distributions using solid phase reversible immobilization (SPRI). This size selection captures DNA fragments of the necessary length to enable the generation of overlapping reads when sequenced from both ends. The lower-quality ends of mated reads were then used to produce a high-quality consensus sequence in the region of overlap. The fraction of composite reads that could be assigned to a taxon was similar to those from 454-FLX, despite the slightly shorter average read length of the composite Illumina reads. This technique successfully demonstrates a practical and economical alternative to 454-FLX for metagenomics. In addition, a scalable, fully automated process for creating sequence-ready, barcoded libraries of 16S rDNA for microbial diversity studies was developed for the Illumina platform. This process will enable sequencing of hundreds of environmental samples on a single Illumina flowcell, greatly decreasing the cost per sample while providing thousands of short-reads for microbial ecology studies. The incorporation of error-correcting, short DNA "barcodes" (also called tags or indexes) during polymerase chain reaction (PCR) amplification of the 16S sequence facilitates sample multiplexing. This process also utilizes the SPRI method to replace column-based reaction clean-ups, enabling the library preparation procedure to be performed almost entirely by a robotic liquid handling workstation. Finally, two unique PCR primer systems (primer-clipping and primer-skipping) were engineered to increase the informative read length of 16S sequence by either cutting the known universal tract out of the final-product to be sequenced, or by omitting sequencing of the universal regions using specially-crafted primers designed to be compatible with Illumina platform conditions. By applying both the overlapping-read technique and multiplexed 16S library preparation workflow, a streamlined approach for efficient gene and species discovery has been assembled to accommodate new metagenomic applications for the Illumina sequencing platform.
by Matthew Christopher Blackburn.
S.M.
Dias, Joana Miloski. „Caracterização da microbiota envolvida nos processos aeróbios (lodos ativados) e anaeróbios (UASB) de uma indústria de alimentos“. Universidade do Estado do Rio de Janeiro, 2015. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=8792.
Der volle Inhalt der QuelleThe increasing concentration of nutrients in receiving water bodies, especially nitrogen and phosphorus originating from domestic and industrial effluent discharges can cause eutrophication. In order to avoid that, the effluents must be properly treated for nutrients removal in wastewater treatment plants prior discharge. However, the role played by various groups of microorganisms found in wastewater treatment systems is not completely understood due to the complexity of interactions. This study aimed to characterize the structure and dynamics of microbial community (with focus on bacteria involved in the nitrogen cycle and microfauna) and evaluate the biological activity of aerobic and anaerobic reactors for wastewater treatment operated at a food industry. The physical and chemical parameters of the treatment plant were monitored. At the same time, hybridization in situ fluorescent assessed the structure and dynamics of bacterial community involved in the nitrogen cycle. The microfauna in the aerobic reactor were characterized and classified according to the Sludge Biotic Index. The sludge biological activity was assessed by respirometry assays and correlations were made between the microbiota found in the aerobic reactor and selected physicochemical parameters. The physical and chemical parameters analysed complied with the limits allowed by the federal and state regulations and parameters Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD) and Kjeldahl nitrogen were reduced 99.8%, 99.6% and 74.9%, respectively. It was found the presence of both nitrite-oxidizing and ammonia-oxidizing bacteria in both reactors and in each sampling point within the reactors. Pseudomonas fluorescens bacteria also occurred in all collection points of both reactors. Among the microorganism groups observed in the activated sludge, crawling ciliates were the most frequent, followed by tecamoebians, rotifers, ciliates sessile, free natant ciliates, flagellates and other invertebrates. In addition, there was no difference between the densities of the groups found in Points 1 and 2 in the aerobic reactor and the Sludge Biotic Index was found equal to 8 (class I). The similarity between the presented Oxygen Consumption Rate of items 1 and 2 as well as the Oxygen Consumption Rate particularly between points 1 and 2 suggest that oxygen is distributed evenly within the aeration tank, causing the microorganisms to have similar growth conditions. The free natant ciliates were positively correlated with COD and BOD5 and sessile ciliates showed a negative correlation with the COD and the BOD5. Rotifers were negatively correlated with Suspended Volatile Solids in the aerobic reactor. Crawling ciliates, rotifers and the tecamoebians were positively correlated with the total microorganisms found in the aerobic reactor. The free natant ciliates showed a negative correlation with the sessile ciliates, total bacteria, Nitrobacter and other bacteria and a positive correlation with other invertebrates. The flagellates were negatively correlated with the total bacteria, while other bacteria were positively correlated. The other invertebrates showed a negative correlation with Nitrobacter.
Jo, Charles. „A co-culture microplate platform to quantify microbial interactions and growth dynamics“. Thesis, 2019. https://hdl.handle.net/2144/37987.
Der volle Inhalt der Quelle2020-08-30T00:00:00Z
„Machine Learning-based Analysis of the Relationship Between the Human Gut Microbiome and Bone Health“. Master's thesis, 2020. http://hdl.handle.net/2286/R.I.63035.
Der volle Inhalt der QuelleDissertation/Thesis
Masters Thesis Electrical Engineering 2020
„Signal Processing and Machine Learning Techniques Towards Various Real-World Applications“. Doctoral diss., 2018. http://hdl.handle.net/2286/R.I.51580.
Der volle Inhalt der QuelleDissertation/Thesis
Doctoral Dissertation Electrical Engineering 2018
Krom, Russell-John. „Bacteriophage technologies and their application to synthetic gene networks“. Thesis, 2015. https://hdl.handle.net/2144/13726.
Der volle Inhalt der QuelleChen, Sway Peng. „Novel genetic engineering tools for functional alteration of mammalian gut microbiomes“. Thesis, 2019. https://doi.org/10.7916/d8-0kjz-ca53.
Der volle Inhalt der QuelleMarques, Francisca Alexandra Morais. „Interaction of Chitosan Microspheres with Human Gastrointestinal Microbiote“. Master's thesis, 2018. https://hdl.handle.net/10216/116817.
Der volle Inhalt der QuelleMarques, Francisca Alexandra Morais. „Interaction of Chitosan Microspheres with Human Gastrointestinal Microbiote“. Dissertação, 2018. https://repositorio-aberto.up.pt/handle/10216/116817.
Der volle Inhalt der QuelleLopes, Ana Rita Rego. „towards a sustainable rice culture: the role of microbiota“. Doctoral thesis, 2013. https://repositorio-aberto.up.pt/handle/10216/73989.
Der volle Inhalt der QuelleLopes, Ana Rita Rego. „towards a sustainable rice culture: the role of microbiota“. Tese, 2013. https://repositorio-aberto.up.pt/handle/10216/73989.
Der volle Inhalt der QuelleGregório, Ana Marisa Magalhães. „Análise da microbiota da água da rede de abastecimento de uma unidade de produção de tintas“. Master's thesis, 2020. https://hdl.handle.net/10216/132887.
Der volle Inhalt der QuelleGregório, Ana Marisa Magalhães. „Análise da microbiota da água da rede de abastecimento de uma unidade de produção de tintas“. Dissertação, 2020. https://hdl.handle.net/10216/132887.
Der volle Inhalt der QuelleSilva, João Carlos Pinho da. „High Fructose Feeding and Hepatic Fatty Liver Disease Inflammation: The Role of Intestinal Microbiota“. Doctoral thesis, 2020. http://hdl.handle.net/10316/95013.
Der volle Inhalt der QuelleChronic metabolic diseases related to obesity and lifestyle are imposing an ever-increasing burden on healthcare worldwide. Incidences of non-alcoholic fatty liver disease (NAFLD) and Type-2 diabetes (T2D) have been rising particularly rapidly in Western Societies, showing strong associations with sedentary lifestyle and excessive caloric intake in relation to daily expenditure. A significant fraction of this hypercaloric intake is accounted by sugar, in particular fructose, present in processed food and sweetened beverages. This diet promotes weight gain, insulin resistance and dyslipidemia thereby providing the foundations for NAFLD and T2D development. In addition to directly disrupting the control of systemic carbohydrate and lipid metabolism, such diets may also mediate these effects indirectly via the gut microbiome. The gut microbiome is a complex ecosystem that is normally in a symbiotic relationship with the host and having a key role in nutrient processing and energy harvest. In obesity-related diseases such as NAFLD and T2D, dysbiotic alterations in the microbiome composition, its metabolic endproducts, and its interactions with host tissues, are implicated in their pathogenesis. The first part of this work aimed to study the effects of a diet high in simple sugars on the composition of the intestinal microbiome and its metabolite products in mouse models. It was hypothesized that dietary glucose and fructose have distinct effects on these parameters with focus on the relative abundance of Gram-negative species and alterations in SCFA levels. Three groups of mice were fed over 10 weeks with standard, high glucose or high fructose chow. Fecal samples were periodically collected and the microbiome was profiled by real-time quantitative polymerase chain reaction (qPCR). Fecal metabolites were analyzed by proton nuclear magnetic resonance (1H NMR). On the metabolites content significant differences were also observed with a reduction in beneficial SCFA like butyrate, to be induced by fructose. For the mice fed the high fructose diet, unmetabolized fructose was found in the feces indicating that the intestinal absorption capacity had been saturated and that fructose was available to the entire intestinal microbiome. Mice fed the high fructose diets also showed a shift in microbiome species towards Gram-negative bacteria and decreased fecal levels of butyrate relative to acetate and propionate. An increased abundance of Gram-negative bacteria could promote visceral inflammation through increased abundance and leakage of endotoxin from the intestinal lumen into surrounding tissues. In addition, alterations in microbiome metabolic endproducts such as lactate and short-chain fatty acids (SCFA) can have an impact on intestinal as well as hepatic and peripheral metabolism through direct substrate effects as well as by activation of substrate-specific receptors such as the GPR family. In the second part of the Thesis, the specific contributions of dietary glucose and fructose to hepatic and adipose tissue lipogenesis were determined by integrating 2H-enrichment of triglyceride from deuterated water to provide estimates of de novo lipogenesis (DNL) and glycerol synthesis from all sources with 13C-triglyceride (TG) enrichment from 13C-glucose and fructose tracers to provide specific contributions of each exogenous sugar. In liver, exogenous fructose contributed significantly more to both DNL and glycerol synthesis compared to exogenous glucose. Moreover, fructose promoted the synthesis of saturated fatty acids to a greater degree than that of oleate whereas glucose did not. Fructose also contributed to mesenteric adipose tissue TG synthesis, albeit to a lesser degree than glucose while only glucose contributed to subcutaneous adipose tissue TG synthesis. In conclusion, this dissertation provided new insights on the role of the intestine and visceral adipose tissue in the metabolism of dietary glucose and fructose and has opened two important new lines of research. First, the potential for overflow of fructose into the lower intestine: to what extent does this happen in humans in the Western diet setting and how does this influence microbiome composition and metabolism? In this context, there is evidence that fructose malabsorption in the human population may be more widespread than initially thought. Second, the lipogenic utilization of fructose carbons by mesenteric adipose tissue begs the question of how this sugar became available to these adipocytes. Was it via direct absorption or was it converted beforehand to glucose by intestinal gluconeogenesis? If it was by direct absorption, this implies that mesenteric adipocytes have a capacity for fructose uptake and metabolism. Also, it suggests that mesenteric adipose tissue has some degree of privileged access to nutrients that are absorbed by the intestine.
As doenças metabólicas crónicas associadas a obesidade e estilo de vida representam um encargo significativamente crescente na saúde mundial. Nas sociedades ocidentais, as incidências de fígado gordo não alcoólico (NAFLD) e diabetes tipo 2 (T2D) têm aumentado consideravelmente correlacionando-se com sedentarismo e consumo excessivo de calorias perante o consumo diário. Nestas dietas hipercalóricas, o açúcar é maioritário em especial a frutose, presente em concentrações elevadas nos alimentos processados. Estas condições estimulam o aumento de peso, resistência à insulina e dislipidémia, que estão na base do desenvolvimento de NAFLD e T2D. Para além destas dietas promoverem distúrbios diretos no metabolismo de lípidos e hidratos de carbono, podem derivar indiretamente os mesmos efeitos, através do microbioma intestinal. Este é um ecossistema complexo que normalmente se encontra em simbiose com o hospedeiro, o que é fundamental para o processamento de nutrientes e extração de energia. Alterações às populações microbianas e perda de simbiose, produtos metabólicos dessas espécies e a respetiva interação com vários tecidos do hospedeiro estão na origem das patologias referidas. A primeira parte deste trabalho visou estudar, em modelos de ratinho, o efeito de dietas ricas em açúcares simples, na composição do microbioma intestinal e dos seus produtos metabólicos. A hipótese propunha que a glicose e frutose produzem efeitos distintos, com foco para alterações na abundância relativa de espécies Gram-negativas e nos níveis de ácidos gordos de cadeia curta (SCFA). Três grupos foram alimentados por um período de 10 semanas com 3 tipos de dieta: standard, rica em glucose ou rica em frutose. Periodicamente, recolheram-se amostras fecais e o perfil microbiológico analisado por real-time quantitative polymerase chain reaction (qPCR). Os metabolitos fecais foram analisados por ressonância magnética nuclear de protão (1H NMR). Observaram-se diferenças significativas no conteúdo em metabolitos com uma redução, induzida por frutose, em SCFA benéficos como o butirato. Nos animais alimentados com elevados níveis de frutose, moléculas não metabolizadas deste açúcar foram encontradas nas fezes, indicando uma saturação da absorção intestinal que resulta em maior disponibilidade de frutose para o microbioma. No mesmo grupo de ratinhos verificou-se uma alteração na composição microbiana com maior tendência para espécies Gram-negativas e um decréscimo nas concentrações de butirato em relação a acetato e propionato. A prevalência destas bactérias pode promover inflamação visceral pelo seu crescimento e libertação de endotoxinas do lúmen intestinal para os tecidos circundantes. Adicionalmente, variações nos metabolitos bacterianos como lactato e SCFA podem alterar o metabolismo intestinal, hepático e periférico através de modificações diretas por substratos, como ativação específica de recetores sensíveis a esses, tais como os da família GPR. Na segunda parte desta Tese, foram determinadas as contribuições específicas da glucose e frutose nas dietas, para a lipogénese no fígado e tecido adiposo, através da integração do enriquecimento nos triglicerídeos (TG) em 2H proveniente de água deuterada para quantificação da lipogénese de novo (DNL) e síntese de glicerol gerais, com o enriquecimento nos mesmos TG em 13C proveniente de marcadores 13C-glucose e 13C-frutose para analisar as contribuições específicas destes açúcares exógenos. No fígado, a frutose deteve um contributo significativamente superior para a DNL e síntese de glicerol quando comparada com glucose. Neste contexto, a frutose promoveu a produção de ácidos gordos saturados em maior escala, efeito não verificado com a glucose. No tecido adiposo mesentérico a frutose contribuiu para a síntese de TG embora em menor porção que a glicose. No tecido adiposo subcutâneo apenas a glicose contribuiu para a lipogénese. Em nota conclusiva, esta dissertação apresenta novas evidências no papel do intestino e tecido adiposo visceral no metabolismo da glicose e frutose e estabelece bases para duas novas linhas de investigação. A primeira reporta à saturação de frutose no intestino grosso: em que medida este fenómeno ocorre em humanos sob dietas ocidentais e a influência que terá na composição do microbioma e metabolismo? Existem evidências de que a malabsorção de frutose em humanos poderá ser transversal a um grupo maior de populações que inicialmente esperado. A segunda refere-se à utilização dos carbonos da frutose para lipogénese no tecido adiposo mesentérico em que se questiona por que processo este açúcar fica disponível aos adipócitos. Por via de absorção direta ou através de gluconeogénese intestinal por conversão prévia a glicose? Se se verificar a absorção direta, será demonstrado que os adipócitos mesentéricos são capazes de assimilar e metabolizar frutose inferindo que o tecido adiposo mesentérico possui, em alguma medida, um acesso privilegiado a nutrientes absorvidos pelo intestino.