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A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

ABSTRACT: Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

SUBMITTER: Desai MS

PROVIDER: S-EPMC5131798 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

Desai Mahesh S MS Seekatz Anna M AM Koropatkin Nicole M NM Kamada Nobuhiko N Hickey Christina A CA Wolter Mathis M Pudlo Nicholas A NA Kitamoto Sho S Terrapon Nicolas N Muller Arnaud A Young Vincent B VB Henrissat Bernard B Wilmes Paul P Stappenbeck Thaddeus S TS Núñez Gabriel G Martens Eric C EC

Cell 20161101 5

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pa ...[more]

PMID: 27863247

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Project description:The main purpose of the present study was to assess the effect of soluble and insoluble fiber on colonic bacteria and intestinal barrier function in a piglet model. A total of 24 piglets (25 ± 1 d old; 7.50 ± 0.31 kg) were randomly allotted to 4 treatments: basal diet (control, CON), 1% insoluble dietary fiber (IDF) diet, 1% soluble dietary fiber (SDF) diet, and 0.5% insoluble fiber + 0.5% soluble dietary fiber (MDF) diet. The trial lasted 28 days. SDF-fed piglets showed a higher (P < 0.05) bacterial a-diversity (observed_species, chao1, and ACE) and a higher relative abundance of Proteobacteria and Actinobacteria, Solobacterium, Succinivibrio, Blautia, and Atopobium in colonic digesta than CON, IDF, and MDF groups (P < 0.05). At the same time, Bacteroidetes, Euryarchaeota, Phascolarctobacterium, Coprococcus_1, and Prevotella_1 were significantly increased in the IDF group when compared with CON, SDF, and MDF groups (P < 0.05). Furthermore, Bacteroidetes and Enterobacteriaceae, Selenomonas, Phascolarctobacterium, and Alloprevotella(P < 0.05) were significantly higher in the MDF group than those in the other three groups (P < 0.05). SDF diet increased the concentrations of short-chain fatty acid (SCFA) in colonic digesta (P < 0.05) when compared with the CON group and enhanced weight index of the colon (P < 0.05) than the CON and IDF groups. Furthermore, compared with the CON group, SDF, IDF, and MDF diets all upregulated the mRNA expressions of claudin-1 (CLDN-1) in colonic mucosa (P < 0.05), SDF and IDF diets upregulated the mRNA expressions of mucin 2 (MUC2) (P < 0.05), SDF diet increased mRNA expressions of zonula occludens 1 (ZO-1) and occludin (OCLN), while the IDF group enhanced the secretory immunoglobulin A (sIgA) concentrations (P < 0.05), respectively. IDF and MDF diets decreased expressions of TNF-α(P < 0.05). We concluded that the influence of soluble fiber on colonic microbiota was more extensive than that of insoluble fiber. Moreover, soluble fiber could more effectively improve colonic barrier function by upregulating gene expressions of the gut barrier.

Project description:Background & aimsThe interorgan crosstalk between the liver and the intestine has been the focus of intense research. Key in this crosstalk are bile acids, which are secreted from the liver into the intestine, interact with the microbiome, and upon absorption reach back to the liver. The bile acid-activated farnesoid X receptor (Fxr) is involved in the gut-to-liver axis. However, liver-to-gut communication and the roles of bile acids and Fxr remain elusive. Herein, we aim to get a better understanding of Fxr-mediated liver-to-gut communication, particularly in colon functioning.MethodsFxr floxed/floxed mice were crossed with cre-expressing mice to yield Fxr ablation in the intestine (Fxr-intKO), liver (Fxr-livKO), or total body (Fxr-totKO). The effects on colonic gene expression (RNA sequencing), the microbiome (16S sequencing), and mucus barrier function by ex vivo imaging were analysed.ResultsDespite relatively small changes in biliary bile acid concentration and composition, more genes were differentially expressed in the colons of Fxr-livKO mice than in those of Fxr-intKO and Fxr-totKO mice (3272, 731, and 1824, respectively). The colons of Fxr-livKO showed increased expression of antimicrobial genes, Toll-like receptors, inflammasome-related genes and genes belonging to the 'Mucin-type O-glycan biosynthesis' pathway. Fxr-livKO mice have a microbiome profile favourable for the protective capacity of the mucus barrier. The thickness of the inner sterile mucus layer was increased and colitis symptoms reduced in Fxr-livKO mice.ConclusionsTargeting of FXR is at the forefront in the battle against metabolic diseases. We show that ablation of Fxr in the liver greatly impacts colonic gene expression and increased the colonic mucus barrier. Increasing the mucus barrier is of utmost importance to battle intestinal diseases such as inflammatory bowel disease, and we show that this might be done by antagonising FXR in the liver.Lay summaryThis study shows that the communication of the liver to the intestine is crucial for intestinal health. Bile acids are key players in this liver-to-gut communication, and when Fxr, the master regulator of bile acid homoeostasis, is ablated in the liver, colonic gene expression is largely affected, and the protective capacity of the mucus barrier is increased.

Dataset Information

A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

Publications

A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

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