Impact Of Gut Microbiota Research Articles

Abstract 845: Diet stamps on bugs: early life dietary energy intake impacts gut microbiota

Abstract The complex and dynamic interactions between diet, gut microbiota (GM) structure and function, and colon carcinogenesis are only beginning to be elucidated. We examined the colonic microbiota and aberrant crypt foci (ACF) in C57BL/6N female mice fed various dietary interventions (control, energy restricted and high-fat) provided during two phases (initiation and progression) of azoxymethane (AOM)-induced early colon carcinogenesis. During progression (wks. 22- 60), a high-fat diet enhanced ACF formation compared to a control or energy restricted diet. In contrast, energy restriction during initiation phase (wks. 3-21) enhanced ACF burden at 60 weeks, regardless of the diet in progression phase. Alterations in GM structure during the initiation phase diet were partially maintained after changing diets during the progression phase. However, diet during the progression phase had major effects on the mucosal GM that energy restriction in progression phase increased Firmicutes and reduced Bacteroidetes compared to a high-fat diet, regardless of initiation phase diet, suggesting that diet may have both transient effects as well as a lasting impact on GM composition. Integration of early life and adult dietary impacts on the colonic microbial structure and function with host molecular processes involved in colon carcinogenesis will be key to defining preventive strategies. Citation Format: Jinyu Xu, Jeffrey Galley, Michael Bailey, Jennifer Thomas-Ahner, Steven Clinton, Susan Olivo-Marston. Diet stamps on bugs: early life dietary energy intake impacts gut microbiota. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 845.

Impact of gut microbiota on the fly's germ line.

Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants. We further show that the main impact on oogenesis is linked to the lack of gut Acetobacter species, and we identify the Drosophila Aldehyde dehydrogenase (Aldh) gene as an apparent mediator of repressed oogenesis in Acetobacter-depleted flies. The finding of interactions between the gut microbiota and the germ line has implications for reproduction, developmental robustness and adaptation.

Gut microbiota impact on stroke outcome: Fad or fact?

Microbiota and its contribution to brain function and diseases has become a hot topic in neuroscience. We discuss the emerging role of commensal bacteria in the course of stroke. Further, we review potential pitfalls in microbiota research and their impact on how we interpret the available evidence, emerging results, and on how we design future studies.

A polyphenol-rich fraction obtained from table grapes decreases adiposity, insulin resistance and markers of inflammation and impacts gut microbiota in high-fat-fed mice

The objective of this study was to determine if consuming an extractable or nonextractable fraction of table grapes reduced the metabolic consequences of consuming a high-fat, American-type diet. Male C57BL/6J mice were fed a low fat (LF) diet, a high fat (HF) diet, or an HF diet containing whole table grape powder (5% w/w), an extractable, polyphenol-rich (HF-EP) fraction, a nonextractable, polyphenol-poor (HF-NEP) fraction or equal combinations of both fractions (HF-EP+NEP) from grape powder for 16weeks. Mice fed the HF-EP and HF-EP+NEP diets had lower percentages of body fat and amounts of white adipose tissue (WAT) and improved glucose tolerance compared to the HF-fed controls. Mice fed the HF-EP+NEP diet had lower liver weights and triglyceride (TG) levels compared to the HF-fed controls. Mice fed the HF-EP+NEP diets had higher hepatic mRNA levels of hormone sensitive lipase and adipose TG lipase, and decreased expression of c-reactive protein compared to the HF-fed controls. In epididymal (visceral) WAT, the expression levels of several inflammatory genes were lower in mice fed the HF-EP and HF-EP+NEP diets compared to the HF-fed controls. Mice fed the HF diets had increased myeloperoxidase activity and impaired localization of the tight junction protein zonula occludens-1 in ileal mucosa compared to the HF-EP and HF-NEP diets. Several of these treatment effects were associated with alterations in gut bacterial community structure. Collectively, these data demonstrate that the polyphenol-rich, EP fraction from table grapes attenuated many of the adverse health consequences associated with consuming an HF diet.

Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus.

Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM, and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC p< = 1.0e-02). Specifically, lower stool Bacteroidaceae, Clostridiales XIV, Lachnospiraceae, Ruminococcacae and higher Enterococcaceae and Enterobacteriaceae were seen in hospitalized patients. Concomitant DM impacted microbiota UNIFRAC (stool, p = 0.003, mucosa,p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations.

The impact of gut microbiota on brain and behaviour

The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk

Gut microbiota has been recently established to have a contributory role in the development of cardiometabolic disorders, such as atherosclerosis, obesity, and type 2 diabetes. Growing interest has focused on the modulation of gut microbiota as a therapeutic strategy in cardiovascular diseases and metabolic disorders. In this paper, we have reviewed the impact of gut microbiota on metabolic disorders and cardiovascular disease risk, focusing on the newest findings in this field.

Habitat fragmentation is associated to gut microbiota diversity of an endangered primate: implications for conservation.

The expansion of agriculture is shrinking pristine forest areas worldwide, jeopardizing the persistence of their wild inhabitants. The Udzungwa red colobus monkey (Procolobus gordonorum) is among the most threatened primate species in Africa. Primarily arboreal and highly sensitive to hunting and habitat destruction, they provide a critical model to understanding whether anthropogenic disturbance impacts gut microbiota diversity. We sampled seven social groups inhabiting two forests (disturbed vs. undisturbed) in the Udzungwa Mountains of Tanzania. While Ruminococcaceae and Lachnospiraceae dominated in all individuals, reflecting their role in extracting energy from folivorous diets, analysis of genus composition showed a marked diversification across habitats, with gut microbiota α-diversity significantly higher in the undisturbed forest. Functional analysis suggests that such variation may be associated with food plant diversity in natural versus human-modified habitats, requiring metabolic pathways to digest xenobiotics. Thus, the effects of changes in gut microbiota should not be ignored to conserve endangered populations.

Microbiota Differences in Infancy: Lasting Impacts on Metabolism and Immunity

The impact of gut microbiota on human health begins at birth, and may be influenced by factors such as mode of delivery and early infant diet, according to several researchers who presented recent findings during the 2015 ASM General Meeting held in New Orleans last May. These early influences on microbiome composition can have lasting consequences, particularly on metabolism and immunity, they say. While some researchers document differences in microbial communities, others pinpoint particular species and mechanisms that control host responses, which may prove useful in treating metabolic and immune diseases.

Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut.

ABSTRACTGut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis.

A Review of Applied Aspects of Dealing with Gut Microbiota Impact on Rodent Models.

The gut microbiota (GM) affects numerous human diseases, as well as rodent models for these. We will review this impact and summarize ways to handle this challenge in animal research. The GM is complex, with the largest fractions being the gram-positive phylum Firmicutes and the gram-negative phylum Bacteroidetes. Other important phyla are the gram-negative phyla Proteobacteria and Verrucomicrobia, and the gram-positive phylum Actinobacteria. GM members influence models for diseases, such as inflammatory bowel diseases, allergies, autoimmunity, cancer, and neuropsychiatric diseases. GM characterization of all individual animals and incorporation of their GM composition in data evaluation may therefore be considered in future protocols. Germfree isolator-housed rodents or rodents made virtually germ free by antibiotic cocktails can be used to study diverse microbial influences on disease expression. Through subsequent inoculation with selected strains or cocktails of microbes, new "defined flora" models can yield valuable knowledge on the impact of the GM, and of specific GM members and their interactions, on important disease phenotypes and mechanisms. Rodent husbandry and microbial quality assurance practices will be important to ensure and confirm appropriate and research relevant GM.

Pomegranate ellagitannins stimulate growth of gut bacteria in vitro: Implications for prebiotic and metabolic effects

The present study investigated the effect of pomegranate extract (POMx) and pomegranate juice (POM juice) on the growth of major groups of intestinal bacteria: Enterobacteriaceae, Bacteroides fragilis group, clostridia, bifidobacteria, and lactobacilli, and the utilization of pomegranate polyphenols by Bifidobacterium and Lactobacillus. The total phenolic content of the pomegranate extract and juice was determined using the Folin-Ciocalteau colorimetric method and reported as gallic acid equivalent (GAE). The polyphenol composition was determined by HPLC. Stool specimens were incubated with 400, 100, and 25 μg/ml GAE POMx and POM juice and subjected to selective culture. Bifidobacterium and Lactobacillus strains were incubated with 400 μg/ml GAE POMx and POM juice and metabolites were analyzed. POMx and POM juice increased the mean counts of Bifidobacterium and Lactobacillus and significantly inhibited the growth of B. fragilis group, clostridia, and Enterobacteriaceae in a dose–response manner. Bifidobacterium and Lactobacillus utilized ellagic acid and glycosyl ellagic acid but little or no punicalin was utilized. Neither POMx nor POM juice was converted to urolithins by the test bacteria or the in vitro stool cultures. The effect of pomegranate on the gut bacteria considered to be beneficial (Bifidobacterium and Lactobacillus) suggests that pomegranate may potentially work as a prebiotic. The concept that polyphenols such as those in pomegranate impact gut microbiota populations may establish a new role for polyphenols in human health.

California Table Grape Consumption Reduces Adiposity, Hepatic Triglycerides, Lipogenic Gene Expression, and Abundance of Sulfidogenic Bacteria in Mice Fed Butter Fat

This study examined the extent to which consuming polyphenol‐rich, California table grapes (3 or 5%, w/w) reduces adiposity, hepatic steatosis, markers of inflammation or lipid metabolism, or impacts gut microbiota in male C57BL/6J mice fed a butter‐rich diet for 11 weeks. Total body and inguinal fat content were reduced in mice fed grapes at both levels compared to their high‐fat, sugar controls. Liver weights, triglycerides, and expression of lipogenic Gpat1 were decreased in mice fed 5% grapes compared to 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of the lipogenic genes Pparg2, Scd1, Fabp4, and Gpat1 compared to 3% controls. In white adipose tissue (WAT), mice fed 5% grapes had decreased mRNA levels of the lipogenic gene Agpat2 compared to controls. Although grape feeding had only a minor impact on markers of inflammation in WAT or intestine, 3% grapes decreased the intestinal abundance of sulfidogenic Desulfobacter spp. and the Bilophila wadsworthia‐specific dissimilatory sulfite reductase gene, and tended to increase the abundance of the beneficial bacterium Akkersmansia muciniphilia compared to controls. Notably, grape feeding attenuated the high fat‐induced impairment in localization of the intestinal tight junction protein ZO‐1. These data indicate that some of the adverse health consequences of consuming a diet rich in saturated fat can be attenuated by table grape consumption. Funded by the California Table Grape Commission.

Impact of gut microbiota on host physiology and pathology

Impact of gut microbiota on host physiology and pathology

Intestinal mucosal tolerance and impact of gut microbiota to mucosal tolerance.

The mucosal barriers are very sensitive to pathogenic infection, thereby assuming the capacity of the mucosal immune system to induce protective immunity to harmful antigens and tolerance against harmless substances. This review provides current information about mechanisms of induction of mucosal tolerance and about impact of gut microbiota to mucosal tolerance.

Gut-Brain Axis: The Role of Gut Microbiota in the Psychiatric Disorders

Bagirsak mikrobiyotasi beyin ve bagirsak arasinda karsilikli bir iliski olusturarak insan sagligi uzerinde temel ve onemli bir rol oynar. Obesite, diyabet gibi metabolik hastaliklar ve sizofreni, otizm, anksiye-te, depresyon gibi neuropsikiyatrik bozukluklarla bagirsak mikrobiyotasi arasinda baglanti olduguna iliskin guclu kanitlar vardir. Yeni arastirmalar gastrointestinal sistemde yasayan dost, zararli ve probiyotik mikroorganizmalarin bagisiklik sistemini, noral yolaklari ve pesi sira merkezi sinir sistemini uyardigini ortaya koymaktadir. Bu mikroorganizmalar bagirsak beyin ekseninde rol oynayan gama-aminobutirik asit ve serotonin gibi noroaktif maddeleri uretmektedir. Preklinik hayvan deneyleri bazi probiyotik bakterilerin anksiyolitik ve antidepresan etkiye sahip oldugunu gostermektedir. Bu maka-lede bagirsak mikrobiyotasinin beyin, davranis ve psikiyatrik bozukluklar uzerine etkisi gozden gecirilmistir.

Gut microbiome and anticancer immune response: really hot Sh*t!

The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism.

A polyphenol‐rich sorghum cereal alters colon microbiota and plasma metabolites in overweight subjects (270.7)

Diet has the potential to impact gut microbiota and metabolism, with implications for obesity and inflammation. We have shown that polyphenol‐rich sumac sorghum (contains condensed tannins) alters microbial populations and metabolites in rats. The goal of this study was to determine if similar effects occur in overweight subjects predisposed to metabolic syndrome (MS). Subjects (n=24) were randomized in a crossover design with high (100 g/d) and low (50 g/d) intakes (4 wk) of sumac sorghum cereal incorporated in their normal diets. Sumac sorghum induced compositional changes in the fecal microbiota, such as an increase (q=0.076) in anti‐inflammatory Faecalibacterium prausnitzii species. Untargeted metabolomic analysis of plasma revealed reductions in amino acid (AA) metabolites as well as increases in microbially‐derived aromatic AA and polyphenol metabolites. 3‐hydroxyhippurate, a product of chlorogenic acid metabolism shown to be reduced in individuals with impaired glucose tolerance, was increased (q=0.0145) following sumac sorghum consumption. Three gamma‐glutamyl AAs produced by gamma‐glutamyl transferase, a biomarker for MS and cardiovascular risk, were decreased (q&lt;0.05) with the 100 g intake. These data suggest sumac sorghum beneficially modulates gut bacteria and their metabolites, which may contribute to reduced inflammation and improved glucose sensitivity.Grant Funding Source: Supported by United Sorghum Checkoff Program R0002‐11.

Dietary fatty acid composition modulates parallel shifts in the metabolic profiles of mice and gut microbiota populations (637.7)

Recent research showed that dietary fat impacts gut microbiota (GM) composition with consequences for host metabolism, particularly in the case of saturated fatty acids (SFA). However, little is known about the impact of other types of fatty acids (FA) on the interaction between GM and host. In this study, we evaluated the impact of diets enriched in health‐promoting polyunsaturated fatty acids (PUFA) or highly unsaturated fatty acids (HUFA) in comparison to SFA on host‐GM interactions. C57Bl/6 mice were placed on normal‐fat (7%) diets with the lipid portion enriched in one of the following: SFA, PUFA, HUFA, or a SFA/HUFA mixture. SFA increased body and liver weight, and liver triglycerides compared to the HUFA‐containing diets. HUFA resulted in the lowest amount of total liver FA and the highest amount of fecal excretion. In the liver, FA synthase and steroyl‐CoA desaturase expression was increased with SFA and PUFA compared to HUFA‐containing diets, while expression of Lipocalins 2 and 13 showed the opposite trend. In the gut, Bacteroides were significantly increased in the SFA/HUFA diet compared to the other three diets. Bifidobacteria were increased in the mice fed PUFA and HUFA‐enriched diets. In conclusion, dietary PUFA and, especially, HUFA enrichment resulted in beneficial changes in metabolic parameters and, speculatively, GM. Continuing research focuses on determining the relationship between the two.Grant Funding Source: Supported by University of Nebraska Agricultural Research Division Strategic Research Initiatives

Irritable bowel syndrome, inflammatory bowel disease and the microbiome

Purpose of reviewThe review aims to update the reader on current developments in our understanding of how the gut microbiota impact on inflammatory bowel disease and the irritable bowel syndrome. It will also consider current efforts to modulate the microbiota for therapeutic effect.Recent findingsGene polymorphisms associated with inflammatory bowel disease increasingly suggest that interaction with the microbiota drives pathogenesis. This may be through modulation of the immune response, mucosal permeability or the products of microbial metabolism. Similar findings in irritable bowel syndrome have reinforced the role of gut-specific factors in this ‘functional’ disorder. Metagenomic analysis has identified alterations in pathways and interactions with the ecosystem of the microbiome that may not be recognized by taxonomic description alone, particularly in carbohydrate metabolism. Treatments targeted at the microbial stimulus with antibiotics, probiotics or prebiotics have all progressed in the past year. Studies on the long-term effects of treatment on the microbiome suggest that dietary intervention may be needed for prolonged efficacy.SummaryThe microbiome represents ‘the other genome’, and to appreciate its role in health and disease will be as challenging as with our own genome. Intestinal diseases occur at the front line of our interaction with the microbiome and their future treatment will be shaped as we unravel our relationship with it.