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Author: Megan Rene Sanctuary Publisher: ISBN: 9781369615975 Category : Languages : en Pages :
Book Description
My research interest is in the role of the gut in overall health with a focus on the role of certain dietary components (including fiber and protein) on microbial composition and activity, gut barrier function, and inflammation. The gastrointestinal (GI) tract must properly digest and absorb nutrients, provide a barrier between environmental pathogens/toxins and the body, and house a balanced immune system that properly discriminates between harmful and beneficial substances/microorganisms. Break down in any one of these functions results in suboptimal health or disease. Most of the research concerning gut microbiota-diet interactions focuses on dietary carbohydrate, especially fiber. Little is known about the metabolism of dietary protein in the distal gut and subsequent effects on host health. Protein digestion has a major impact on amino acid absorption/bioavailability and downstream effects on the microbiota, immune system and colonocyte health; protein digestion and absorption may be compromised in some individuals and not all proteins are easily digested. Increased levels of protein in the colon have numerous potential causes including excessive protein consumption, low protein digestibility (affected by source and processing) as well as low inherent digestive capacity of the consumer. Several studies have shown that increased levels of protein in the colon leads to increased levels of protein-metabolizing (putrefactive) bacteria, reduced levels of fiber-fermenting (saccharolytic) bacteria, reduced bacterial diversity as well as increased levels of putrefactive metabolites in the colon. These metabolites have been associated with inflammatory bowel diseases such as ulcerative colitis (UC). The effects of these metabolites on host physiology have been studied using mainly in vitro models and have been shown to increase intestinal permeability and reduce overall health of colonocytes (Figure 1.1). However, it is unknown whether excess consumption of protein with low digestibility, coupled with reduced digestive capacity, leads to increased intestinal permeability resulting in inflammation and poor overall gut health in vivo. In addition, direct links between the concentrations of toxic putrefactive metabolites in stool and urine, and numbers of protein metabolizing bacteria in stool to specific health changes (e.g. inflammation, tissue damage) and long term health outcomes remain unknown.The focus of this research project lies on two specific populations that experience reduced digestive capacity and who tend to consume proteins with low digestibility. Human infants are born with an immature gut and thus low inherent digestive capacity; those who are formula fed consume high levels of indigestible proteins. Together, these factors may contribute to the microbial dysbiosis and increased incidence of diarrhea experienced by formula fed compared to breastfed infants. Therefore, cell culture experiments assessing intestinal permeabilization in response to certain dietary peptides was performed. Results showed that human milk is capable of reducing intestinal permeability in the absence of immune and microbiota mechanisms. Furthermore, human milk protects intestinal epithelial cells from LPS-induced increases in intestinal permeability. In addition, piglet feeding studies were conducted to assess the effect of consumption of diets high in heat-damaged milk proteins, like those found in formula, on markers of gut health including intestinal permeability, histopathology and diarrhea incidence. Results showed that piglets consuming diets high in partially hydrolyzed milk proteins experience increased intestinal permeability, higher ileum and colon histopathology scores and high incidence of diarrhea compared to piglets consuming diets containing intact proteins. Together, these results support the use of human milk for early infant feeding and further exploration of the role of human milk proteins in modulating intestinal permeability.Children with autism also experience GI dysfunction and immune abnormalities coupled with microbial dysbiosis. Therefore, we conducted a randomized, double-blind, controlled clinical trial assessing tolerability and efficacy of combination treatment with the probiotic Bifidobacterium longum subsp infantis (B. infantis) and bovine colostrum product (BCP) in children with ASD and GI symptoms compared to BCP alone. Results showed that both treatments were well tolerated in this cohort with gassiness and lethargy as the most commonly reported mild side effects. We also found overall improvement in GI function as evidenced by normalization of stool consistency, reduced frequency of GI symptoms, reduction in occurrence of certain aberrant behaviors, lowered percentage of lymphocytes expressing IL-13 (combination treatment) and TNF-[alpha] (BCP only treatment) and decreased fecal ethanol levels with treatment. For most outcome measures, there were trends for improvement with both treatments and in some cases, there were significant improvements for each of the treatments. At this point, we can cannot conclude that one treatment was more effective than the other due to low sample size and high heterogeneity of initial GI symptoms. Further studies with larger sample size with specific recruitment for certain GI symptoms are necessary to gain a mechanistic understanding of these outcomes.In addition, there is some evidence that populations with a fragile gut, especially children with autism and infants, have impaired digestive and/or absorptive capacity. Therefore, exploration of the effect of increased protein fermentation in the distal gut on microbial composition and metabolism, inflammation, intestinal permeability and general gut health will provide preliminary evidence to support mechanistic investigation of these processes in susceptible cohorts. This preliminary study will allow us to develop the tools and protocols to examine the effects of other variables such as effect of protein source (structure) and processing techniques (such as pasteurization), weaning protocol (age and duration of weaning), and other forms of digestive insufficiency (pancreatic insufficiency, chemotherapy) on gut health.
Author: Megan Rene Sanctuary Publisher: ISBN: 9781369615975 Category : Languages : en Pages :
Book Description
My research interest is in the role of the gut in overall health with a focus on the role of certain dietary components (including fiber and protein) on microbial composition and activity, gut barrier function, and inflammation. The gastrointestinal (GI) tract must properly digest and absorb nutrients, provide a barrier between environmental pathogens/toxins and the body, and house a balanced immune system that properly discriminates between harmful and beneficial substances/microorganisms. Break down in any one of these functions results in suboptimal health or disease. Most of the research concerning gut microbiota-diet interactions focuses on dietary carbohydrate, especially fiber. Little is known about the metabolism of dietary protein in the distal gut and subsequent effects on host health. Protein digestion has a major impact on amino acid absorption/bioavailability and downstream effects on the microbiota, immune system and colonocyte health; protein digestion and absorption may be compromised in some individuals and not all proteins are easily digested. Increased levels of protein in the colon have numerous potential causes including excessive protein consumption, low protein digestibility (affected by source and processing) as well as low inherent digestive capacity of the consumer. Several studies have shown that increased levels of protein in the colon leads to increased levels of protein-metabolizing (putrefactive) bacteria, reduced levels of fiber-fermenting (saccharolytic) bacteria, reduced bacterial diversity as well as increased levels of putrefactive metabolites in the colon. These metabolites have been associated with inflammatory bowel diseases such as ulcerative colitis (UC). The effects of these metabolites on host physiology have been studied using mainly in vitro models and have been shown to increase intestinal permeability and reduce overall health of colonocytes (Figure 1.1). However, it is unknown whether excess consumption of protein with low digestibility, coupled with reduced digestive capacity, leads to increased intestinal permeability resulting in inflammation and poor overall gut health in vivo. In addition, direct links between the concentrations of toxic putrefactive metabolites in stool and urine, and numbers of protein metabolizing bacteria in stool to specific health changes (e.g. inflammation, tissue damage) and long term health outcomes remain unknown.The focus of this research project lies on two specific populations that experience reduced digestive capacity and who tend to consume proteins with low digestibility. Human infants are born with an immature gut and thus low inherent digestive capacity; those who are formula fed consume high levels of indigestible proteins. Together, these factors may contribute to the microbial dysbiosis and increased incidence of diarrhea experienced by formula fed compared to breastfed infants. Therefore, cell culture experiments assessing intestinal permeabilization in response to certain dietary peptides was performed. Results showed that human milk is capable of reducing intestinal permeability in the absence of immune and microbiota mechanisms. Furthermore, human milk protects intestinal epithelial cells from LPS-induced increases in intestinal permeability. In addition, piglet feeding studies were conducted to assess the effect of consumption of diets high in heat-damaged milk proteins, like those found in formula, on markers of gut health including intestinal permeability, histopathology and diarrhea incidence. Results showed that piglets consuming diets high in partially hydrolyzed milk proteins experience increased intestinal permeability, higher ileum and colon histopathology scores and high incidence of diarrhea compared to piglets consuming diets containing intact proteins. Together, these results support the use of human milk for early infant feeding and further exploration of the role of human milk proteins in modulating intestinal permeability.Children with autism also experience GI dysfunction and immune abnormalities coupled with microbial dysbiosis. Therefore, we conducted a randomized, double-blind, controlled clinical trial assessing tolerability and efficacy of combination treatment with the probiotic Bifidobacterium longum subsp infantis (B. infantis) and bovine colostrum product (BCP) in children with ASD and GI symptoms compared to BCP alone. Results showed that both treatments were well tolerated in this cohort with gassiness and lethargy as the most commonly reported mild side effects. We also found overall improvement in GI function as evidenced by normalization of stool consistency, reduced frequency of GI symptoms, reduction in occurrence of certain aberrant behaviors, lowered percentage of lymphocytes expressing IL-13 (combination treatment) and TNF-[alpha] (BCP only treatment) and decreased fecal ethanol levels with treatment. For most outcome measures, there were trends for improvement with both treatments and in some cases, there were significant improvements for each of the treatments. At this point, we can cannot conclude that one treatment was more effective than the other due to low sample size and high heterogeneity of initial GI symptoms. Further studies with larger sample size with specific recruitment for certain GI symptoms are necessary to gain a mechanistic understanding of these outcomes.In addition, there is some evidence that populations with a fragile gut, especially children with autism and infants, have impaired digestive and/or absorptive capacity. Therefore, exploration of the effect of increased protein fermentation in the distal gut on microbial composition and metabolism, inflammation, intestinal permeability and general gut health will provide preliminary evidence to support mechanistic investigation of these processes in susceptible cohorts. This preliminary study will allow us to develop the tools and protocols to examine the effects of other variables such as effect of protein source (structure) and processing techniques (such as pasteurization), weaning protocol (age and duration of weaning), and other forms of digestive insufficiency (pancreatic insufficiency, chemotherapy) on gut health.
Author: Inés Martínez Ramos Publisher: ISBN: 9781267582324 Category : Digestion Languages : en Pages : 273
Book Description
Vertebrates are associated with trillions of bacteria, with the densest populations residing in the large intestine. The symbiosis between vertebrates and their gut microbiota has resulted in important implications of the gut microbiome on host health. Diet is an important factor that shapes gut microbiota composition, and because of the interplay between host-microbiome-diet, dietary strategies that modulate gut microbiome structure are deemed a relevant tool to improve host health. However, gaps in knowledge exist with respect to these interactions, and it is essential to obtain a mechanistic understanding of how these relations take place to develop successful therapeutic strategies that target the gut microbiome. In order to address these gaps, human trials were performed to assess the impact of primary components of the human diet, resistant starches and whole grains, on the gut microbiota. Overall, the impact of diet was temporal and varied across subjects. Resistant starches substantially modulated the gut bacterial community of the subject population, especially increasing the abundance of Bifidobacterium adolescentis . Ruminococcus bromii , Eubacterium rectale , and Parabacteroides distasonis were also significantly enriched. Dietary incorporation of whole grains increased the proportions of Eubacterium rectale and acetogens such as Blautia wexlerae . Of note, whole grains significantly improved inflammation and glycemic parameters. The shifts in Eubacterium rectale correlated with glycemic improvements. Moreover, distinct abundances of Dialister were determined among subjects that differed in terms of their inflammatory improvement. To gain mechanistic insight on the host-microbe-diet interplay, animal experiments were conducted to evaluate the effects of grain sorghum lipids and plant sterol esters in the context of dyslipidemia. Significant and consistent alterations in gut microbiota composition were detected in both experiments, especially involving shifts in Coriobacteriaceae and Erysipelotrichaceae abundance, which displayed remarkable correlations to host cholesterol markers. Mathematical modeling of these associations revealed them to be inhibitory interactions, suggesting that changes in host metabolism affected gut microbiome structure through an antimicrobial effect of cholesterol, which was conformed in vitro against selected gut microbes. In conclusion, the studies presented in this dissertation allowed new insights on the impact of diet on the gut microbiota and its consequences for health.
Author: Martin J. Blaser, MD Publisher: Henry Holt and Company ISBN: 0805098119 Category : Science Languages : en Pages : 289
Book Description
“In Missing Microbes, Martin Blaser sounds [an] alarm. He patiently and thoroughly builds a compelling case that the threat of antibiotic overuse goes far beyond resistant infections.”—Nature Renowned microbiologist Dr. Martin J. Blaser invites us into the wilds of the human microbiome, where for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the equilibrium and health of our bodies. Now this invisible Eden is under assault from our overreliance on medical advances including antibiotics and caesarian sections, threatening the extinction of our irreplaceable microbes and leading to severe health consequences. Taking us into the lab to recount his groundbreaking studies, Blaser not only provides elegant support for his theory, he guides us to what we can do to avoid even more catastrophic health problems in the future. “Missing Microbes is science writing at its very best—crisply argued and beautifully written, with stunning insights about the human microbiome and workable solutions to an urgent global crisis.”—David M. Oshinsky, author of the Pulitzer Prize-winning Polio: An American Story
Author: Food Forum Publisher: National Academies Press ISBN: 030926586X Category : Medical Languages : en Pages : 197
Book Description
The Food Forum convened a public workshop on February 22-23, 2012, to explore current and emerging knowledge of the human microbiome, its role in human health, its interaction with the diet, and the translation of new research findings into tools and products that improve the nutritional quality of the food supply. The Human Microbiome, Diet, and Health: Workshop Summary summarizes the presentations and discussions that took place during the workshop. Over the two day workshop, several themes covered included: The microbiome is integral to human physiology, health, and disease. The microbiome is arguably the most intimate connection that humans have with their external environment, mostly through diet. Given the emerging nature of research on the microbiome, some important methodology issues might still have to be resolved with respect to undersampling and a lack of causal and mechanistic studies. Dietary interventions intended to have an impact on host biology via their impact on the microbiome are being developed, and the market for these products is seeing tremendous success. However, the current regulatory framework poses challenges to industry interest and investment.
Author: Julia Hill Kemis Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The population of microbes that inhabit the mammalian intestine have profound effects on host physiology. The gut microbiome varies substantially among healthy individuals, and its composition is shaped by a complex interplay of environmental and genetic factors. Alterations in its composition are associated with the development of metabolic diseases, including obesity and type 2 diabetes. Therefore, manipulation of the intestinal microbiome ecosystem is a promising target for emerging therapies. However, it remains largely unknown how host genetics interacts with environmental factors (e.g. diet) to shape microbiota profiles, and how these interactions may contribute to metabolic disease susceptibility. The objective of this thesis research was to investigate the effects of host genetic variation on gut microbiota composition, evaluate how these interactions influence host diet-induced metabolic phenotypes, and to identify genetic variants that influence the abundance of gut microbes. In Chapter 2, I evaluate the relative contributions of host genetics and diet on gut microbiota composition and metabolic phenotypes using a panel of eight genetically diverse inbred mouse strains. In a controlled laboratory environment, I found gut microbiota composition and metabolic phenotypes are shaped by both genetics and diet. Guided by the results of this screen, I went on to demonstrate that in a gnotobiotic mouse model transplantation of genotype-associated microbiota can alter pancreatic islet function and confer sustained metabolic phenotypes despite chronic high-fat high-sucrose (HF/HS) feeding. In Chapter 3, I identify host genetic loci that influence gut microbiota and bile acid profiles. I performed quantitative trait loci (QTL) mapping to find genetic variants associated with abundance of gut microbes and bile acid levels using the Diversity Outbred (DO) mouse stock, which is derived from the eight strains profiled in Chapter 2. I found novel genetic variants associated with both microbial taxa and bile acids, including an association between the intestinal bile acid transporter, Slc10a2, the abundance of Turicibacter sp. and plasma cholic acid levels. Subsequent investigation revealed direct interactions between Turicibacter sp. and bile acids in vitro, supporting a role of genetics in elucidating host-microbe interactions. Together, this thesis work contributes to our understanding of host-microbe interactions and provides a foundation for future mechanistic studies.
Author: Dirk Haller Publisher: Springer ISBN: 3319905457 Category : Medical Languages : en Pages : 356
Book Description
The book provides an overview on how the gut microbiome contributes to human health. The readers will get profound knowledge on the connection between intestinal microbiota and immune defense systems. The tools of choice to study the ecology of these highly-specialized microorganism communities such as high-throughput sequencing and metagenomic mining will be presented. In addition the most common diseases associated to the composition of the gut flora are discussed in detail. The book will address researchers, clinicians and advanced students working in biomedicine, microbiology and immunology.
Author: Heli Jaime Barron Pastor Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Host-microbe interactions are now considered essential for maintaining host health. It is known that short and long term dietary interventions influences the structure and activity of gut bacterial communities. However, our understanding of the forces shaping the gut microbiota is still limited and controversial, and most of the studies of the gut microbiota use the microbiota from faeces as a proxy for the intestinal tract populations. As such, the overarching aim of this thesis is to contribute to the understanding of host-microbiome interactions using an animal model. In this thesis I describe the effect of diet changes on microbial community structure and host-microbiome interactions following 14 weeks on one of the three experimental diets. The diets consisted of a basal diet low in fibre (LF); the basal diet together with 26% cellulose; a difficult to ferment fibre (HF); and the basal diet together with 50% dried cooked red kidney beans (B); a diet relatively high in easily fermentable fibre. These diets were fed to 45, 21 day old female Wistar rats originating from 6 litters for 14 weeks. Diet had little effect on rat growth rates or adult body mass. However, diet had profound effects on gastro-intestinal morphology and dynamics. Caecum size was smallest in animals fed the LF diet, and caecums were about 2x as large in animals fed the B diet, while animals on the HF diet had intermediate-sized caecums. Food transit times were slowest in animals on the B and LF diets and fastest in animals on the HF diets. At the end of the diet experiment, colon and caecum contents were collected when the animals were killed and short chain fatty acids, nitrogen, carbon, as well fibre concentrations were determined. These data showed that the 'chemical' environment of the hindgut varied substantially among animals fed the different diets. E. coli diversity and dynamics were described by characterizing more than three thousand isolates. E. coli diversity was low, and more than 97% of the isolates were represent by three strains: one phylogroup B2 strain and two phylogroup B1 strains. A decline of the frequency of the B2 strain in the animals fed on the bean diet was observed. The faecal microbiota was characterized when the animals were 21 days old, while faecal, caecal and rectal microbial communities characterized at the end of the experiment. 16S amplicon sequencing of the V4 region on the Ion Torrent platform was the approach used to characterize the microbiota. Members of 23 microbial families were detected in communities of the animals before and after 14 weeks on the experimental diets. At the start of the experiment there were significant litter membership effects on the structure of the faecal microbial communities. After 14 weeks on the experimental diets, both litter and diet explained a significant amount of the variation in microbial community structure. There were substantial differences in the microbial communities of the caecum and rectum and the extent of these differences depended on diet and on the time taken for material to move through the hindgut. The outcomes of the present study make a contribution to our understanding of the factors that shape gut microbial communities. Microbial characterization of faecal samples is frequently used as proxy of gut microbiota. However, stool samples are probably most likely representative of the microbial communities in the rectum than other parts of the gastrointestinal tract. Indeed, the findings also throw doubt on the value of faecal community characterization as a means to understand community structure and function in the gastro-intestinal tract. Further, the results of these experiments suggest that efforts attempting to achieve positive health outcomes through diet manipulation may have limited success in general due to among individual differences in microbial community composition, and in how these different communities respond to dietary manipulation.
Author: Edmond Yii-Ming Huang Publisher: ISBN: 9781303231544 Category : Languages : en Pages : 132
Book Description
Over 100 trillion bacteria live in our gastrointestinal tract, comprising an ecosystem that exceeds the number of our cells by over ten-fold and is far more genetically diverse. Countless years of evolutionary pressures have driven these resident microbes, termed gut microbiota, to genetically and functionally evolve in ways that foster a mutualistic relationship with their hosts. For example, gut microbiota are known to subsist on indigestible carbohydrates, metabolizing them into readily-available short-chain fatty acids (SCFAs) beneficial to their host. Over the past decade, a rapid emergence of culture-independent, high-throughput in silico 16S ribosomal RNA sequencing technologies have provided scientists the necessary tools to more deeply and efficiently characterize the gut microbiota. Researchers have uncovered a multitude of critical metabolic, immune, and developmental pathways that are critically affected by gut microbes, which, when awry, have led to diseases that include colon cancer, metabolic syndrome, obesity, asthma, inflammatory bowel diseases, and olther complex immune disorders. We hypothesize that both dietary as well as pharmacologic factors are capable of altering the composition and function of gut microbial communities to mediate effects that contribute physiologically as well as pathophysiologically. In the first study, we demonstrate that the consumption of specific dietary fats alters gut microbiota, which then promotes the expression of inflammatory genes in adipose tissue. This action may be a key step towards setting up the conditional requirements that eventually lead to metabolic disturbances, Type 2 diabetes, and obesity. Our second study explores the pharmacologic mechanisms of action of glucocorticoids which are widely used clinically, albeit their actions are still incompletely understood. We report that chronic exposure to the synthetic glucocorticoid dexamethasone (DEX) reshapes the gut microbiota in a way that affects colonic mucin expression. Our findings suggest that these actions may in part contribute to the anti-inflammatory effects observed in a genetically susceptible mouse model of colitis. Altogether, the studies highlight how susceptible host-microbe interactions can be to dietary and pharmacological influences. These effects can promote host health on the one hand, but, on the other, contribute to the development of disease. We believe this knowledge can be used to our advantage in developing novel diagnostic and therapeutic strategies and for lowering risk of disease.
Author: National Academies of Sciences, Engineering, and Medicine Publisher: National Academies Press ISBN: 0309468698 Category : Science Languages : en Pages : 123
Book Description
A great number of diverse microorganisms inhabit the human body and are collectively referred to as the human microbiome. Until recently, the role of the human microbiome in maintaining human health was not fully appreciated. Today, however, research is beginning to elucidate associations between perturbations in the human microbiome and human disease and the factors that might be responsible for the perturbations. Studies have indicated that the human microbiome could be affected by environmental chemicals or could modulate exposure to environmental chemicals. Environmental Chemicals, the Human Microbiome, and Health Risk presents a research strategy to improve our understanding of the interactions between environmental chemicals and the human microbiome and the implications of those interactions for human health risk. This report identifies barriers to such research and opportunities for collaboration, highlights key aspects of the human microbiome and its relation to health, describes potential interactions between environmental chemicals and the human microbiome, reviews the risk-assessment framework and reasons for incorporating chemicalâ€"microbiome interactions.
Author: Publisher: Academic Press ISBN: 0128096179 Category : Science Languages : en Pages : 346
Book Description
Host-Microbe Interactions, the latest volume in the Progress in Molecular Biology series, provides a forum for the discussion of new discoveries, approaches, and ideas in molecular biology. It contains contributions from leaders in their respective fields, along with abundant references. This volume is dedicated to the subject of host-microbe interactions. Provides the latest research on host-microbe interactions, including new discoveries, approaches, and ideas Contains contributions from leading authorities on topics relating to molecular biology Informs and updates on all the latest developments in the field
Author: Megan Rene Sanctuary
Author: Megan Rene Sanctuary
Author: Inés Martínez Ramos
Author: Martin J. Blaser, MD
Author: Food Forum
Author: Julia Hill Kemis
Author: Dirk Haller
Author: Heli Jaime Barron Pastor
Author: Edmond Yii-Ming Huang
Author: National Academies of Sciences, Engineering, and Medicine
Author: