Mechanisms of inflammation-driven bacterial dysbiosis in the gut.
TL;DR: Summary of studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterob bacterial species in the gut are highlighted.
About: This article is published in Mucosal Immunology.The article was published on 2017-01-01 and is currently open access. It has received 499 citations till now. The article focuses on the topics: Dysbiosis & Gut flora.
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TL;DR: Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
Abstract: The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co-evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
841 citations
TL;DR: Nonantimicrobial alternatives, such as zinc oxide, essential oils, and prebiotics or probiotics, which are currently evaluated to restore intestinal balance and allow a better management of the crucial weaning transition are focused on.
449 citations
TL;DR: The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented, which suggests that well-designed randomized control trials and mouse models are required for further research.
Abstract: Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.
369 citations
Cites background from "Mechanisms of inflammation-driven b..."
...This disruption in the gut mic obiota balance ulti ately results in an alteration of t gut micro flora-associated functions, including alteration of fermentation products such as carbohydr tes, vit mi s, and SCFAs [53], and biochemical proces alteratio s, such as immune equilibrium imbalance [54–56]....
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...This disruption in the gut microbiota balance ultimately results in an alteration of the gut micro flora-associated functions, including alteration of fermentation products such as carbohydrates, vitamins, and SCFAs [53], and biochemical process alterations, such as immune equilibrium imbalance [54–56]....
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...including alteration of fermentation products such as carbohydrates, vitamins, and SCFAs [53], and...
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...Abbreviations IBD, Inflammatory Bowel Disease; CAM, complementary and alternative medicine; CD, Crohn’s disease; DAI, disease activity index; TNBS, trinitrobenzene sulfonic acid; UC, ulcerative colitis; SCFAs, short-chain fatty acids; SFB, segmented filamentous bacteria; IL, interleukin; CRP, C reactive protein, HM, herbal medicine; TCMs, Traditional Chinese herbal medicine; DSS, dextran sulfate sodium, FMT; Fecal microbiota transplantation....
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...Under normal physiological conditions, gut microbiota acts as a homeostatic organ involved in the fermentation of complex undigested polysaccharide polymers, production of short-chain fatty acids (SCFAs), synthesis of certain vitamins, energy production, intestinal mucosa integrity, and preclusion of pathogenic microbes [32–36]....
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TL;DR: Several gut microbial taxa with differential abundance patterns common to IMIDs are identified and may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.
Abstract: Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach. Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance. This study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.
217 citations
TL;DR: ‘gut health’ represents the outcome of the GIT in response to its capacity and ability to respond and adapt to the insults and challenges it encounters and is of obvious interest in the newly-weaned pig.
215 citations
References
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TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
Abstract: The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.
8,410 citations
Journal Article•
TL;DR: The Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far, finding the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals.
Abstract: Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
6,350 citations
University of Évry Val d'Essonne1, Institut national de la recherche agronomique2, Technical University of Denmark3, Barcelona Supercomputing Center4, University of Copenhagen5, University of Tokyo6, University of Miyazaki7, Wageningen University and Research Centre8, Tokyo Institute of Technology9, French Alternative Energies and Atomic Energy Commission10
TL;DR: Three robust clusters (referred to as enterotypes hereafter) are identified that are not nation or continent specific and confirmed in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous.
Abstract: Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
5,566 citations
TL;DR: Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
Abstract: The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
3,967 citations
"Mechanisms of inflammation-driven b..." refers background in this paper
...For example, an increased prevalence of Enterobacteriaceae, including adherent-invasive E. coli (AIEC), is also found in patients with Crohn’s disease or ulcerative colitis, the two forms of IBD.42–46 Despite the increased abundance of E. coli including AIEC in patience with IBD, there is insufficient evidence to substantiate the hypothesis of infectious causes of IBD by AIEC in the gut....
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...coli are observed in human IBD.(44) Conversely, a recent study reported enrichment of E....
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...Increased numbers of mucosaassociated E. coli are observed in human IBD.44 Conversely, a recent study reported enrichment of E. coli in the colons of mice with DSS-induced colonic damage and inflammation, and the growth advantage of E. coli is conferred by elevated mucin-derived sialic acid during inflammation.76 Sialic acid is one of the major carbohydrates in mucins and can be taken up by bacteria lacking de novo biosynthetic pathways for these sugars, such as E. coli, and incorporated into bacterial capsule and lipooligosaccharides.77 During DSS-induced inflammation, the release of sialic acid from mucin was mediated by cecal sialidase activity from Bacteroides vulgatus, which also expanded in the DSS-induced inflamed gut....
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TL;DR: The authors showed that colonisation of mice with a segmented filamentous bacterium (SFB) is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria.
3,860 citations