BackgroundThe dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth.MethodsTo elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan.FindingsLevels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients.InterpretationMucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients.FundJapan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation.
The mechanism underlying transient increases in immunoglobulin (Ig) A concentrations in the cecal contents of rats fed fructo-oligosaccharide (FOS) is unclear. This study was designed to test whether increased IgA concentrations represent one aspect of the inflammatory response to increased permeability induced by FOS in the cecum. Seven-week-old male Wistar rats were fed a fiber-free semipurified diet (FFP) with or without supplemental FOS (60 g/kg diet) for 9 or 58 d [experiment (expt.) 1], 7 d (expt. 2), or 7 or 56 d (expt. 3). In addition to measuring IgA concentrations in cecal content, we assessed gut permeability, inflammatory responses (expt. 1), the number of IgA plasma cells in the cecal lamina propria, polymeric Ig receptor (pIgR) expression in the cecal mucosa (expt. 2), and the condition of the cecal mucus layer (expt. 3). The cecal IgA concentration in the FOS-fed rats was 15-fold higher than that of the rats fed FFP for 9 d ( < 0.05). Gut permeability estimated by urinary chromium-EDTA excretion, bacterial translocation to mesenteric lymph nodes, myeloperoxidase activity, and expression of inflammatory cytokine genes in the cecal mucosa was greater in the FOS-fed rats than in the rats fed FFP for 9 d. These effects were not observed in the rats fed FOS for 58 d (expt. 1). Accompanying the higher cecal IgA concentration, pIgR protein and the number of IgA plasma cells in the cecal mucosa were higher in the FOS-fed rats than in the rats fed FFP for 7 d (expt. 2). Destruction of the mucus layer on the epithelial surface, as evidenced by Alcian blue staining in the cecal sections, was evident in the rats fed FOS for 7 d, but the mucus layer appeared normal in the rats fed FOS for 56 d (expt. 3). These findings suggest that transient increases in cecal IgA concentrations induced by FOS in rats are associated with mucosal inflammation in response to increased gut permeability; these are presumably evoked by disruption of the cecal mucus barrier. The observed responses could contribute to the maturation of the gut immune system.
A number of studies have shown the bifidogenic effects of either probiotic bifidobacteria or inulin, and this bifidogenic shift in the composition of the colonic microbiota is likely the basis for their positive impact on human health. This study aimed to evaluate the effects of synbiotics containing the probiotic bacterium Bifidobacterium animalis subsp. lactis ( B. lactis ) GCL2505 and inulin on the levels of intestinal bifidobacteria compared with B. lactis GCL2505 alone. A randomized, double‐blind, placebo‐controlled, crossover trial was carried out involving 60 healthy subjects with a tendency for constipation using fermented milk containing B. lactis GCL2505 and inulin (synbiotic), only B. lactis GCL2505 (probiotic), and placebo. Fecal samples were collected at the end of each 2‐week intervention period, and the bifidobacterial count was analyzed by quantitative real‐time PCR. The numbers of total bifidobacteria and B. lactis in feces were significantly increased during the probiotic and synbiotic intake periods compared with the placebo intake period. Furthermore, the numbers of total bifidobacteria and endogenous bifidobacteria were significantly higher in the synbiotic intake period compared with the probiotic intake period, while there was no difference in the number of B. lactis . These results suggested that the synbiotics containing B. lactis GCL2505 and inulin had a greater effect on the number of bifidobacteria than a drink containing probiotics alone and could be useful for the improvement of the intestinal environment.
The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as nbutyrate, suggesting that mucin O-glycans act as an endogenous fermentation substrate for nbutyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt + Treg cells and IgA-producing cells in the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) and Crohn's disease (CD), are recurrent inflammatory disorders caused by both genetic and environmental factors [1,2]. Accumulating evidence has demonstrated that abnormal gut microbial composition, termed dysbiosis, plays a role in the pathogenesis and/or exacerbation of IBD in Caucasian patients [3,4]. The gut microbiota of IBD patients is characterized by diminished microbial diversity alongside the underrepresentation of Firmicutes and overrepresentation of Proteobacteria [3,5-8]. These characteristics are evident in the gut microbiota of CD patients, and the severity of dysbiosis in rectal mucosa-associated microbiota correlates well with disease score [7]. Changes in gut microbiota composition are less obvious in UC patients that in CD patients, and their association with IBD pathogenesis has not yet been elucidated [6,8]. Animal experiments have demonstrated that the gut microbiota shapes the host intestinal immune system under physiological conditions by inducing the maturation of gut-associated lymphoid tissues and the differentiation of Th17 and regulatory T cells [9]. In contrast, the gut microbiota drives intestinal inflammation under dysbiosis [10,11]. Similarly, the transplantation of microbiota from CD patients into Il10deficient mice has...
We examined the effects of fructo-oligosaccharides (FOS) on IgA and mucin secretion in the rat cecum after different ingestion periods. Rats were fed a control diet or a diet containing FOS for 1, 2, 4, and 8 wk. FOS ingestion greatly increased IgA and mucin concentrations at 1 and 2 wk, but the effects were disappeared or attenuated at 4 and 8 wk. After 1 wk, FOS induced higher lactobacilli and lactate concentrations and lower cecal pH in the cecum, but the alterations were moderated with the prolonged ingestion accompanying with increasing short-chain fatty acid concentrations. At 1 and 2 wk, FOS increased IgA plasma cells and polymeric immunoglobulin receptor expression in the cecal mucosa and strongly depressed fecal mucinase activities related to the lower cecal pH. These findings may explain the FOS-induced early elevation of IgA and mucin. Clearly, FOS effects on IgA and mucin secretion considerably differ depending on the ingestion period.
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