Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.

A recently developed mechanical method for extracting long bamboo fibres opens the possibility to exploit this new material as reinforcement in composite materials for high end uses. The strength distribution of the fibres was characterized in a novel approach to evaluate the effect of defects introduced by the extraction process as function of different scale variables: fibre length, fibre surface area and fibre volume. The modified Weibull distribution, a practical model requiring only three parameters, described accurately the fibre strength distribution of the fibres at different gauge lengths. The average fibre strength decreased with increasing gauge length, from 943 MPa at L = 1 mm to 733 MPa at L = 40 mm and it was nearly independent of the mean fibre volume. The Weibull shape parameter was found to be 7.6 for all tested fibres, showing low strength variability in comparison with other natural fibres and some synthetic fibres, indicating their high quality.

Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.

Accumulating evidence suggests that deterioration of the gut flora contributes to the pathogenesis of alcoholic liver cirrhosis (ALC). However, the ALC flora profile and its response to probiotic treatment have not been fully examined. This double-blind placebo-controlled study aimed to evaluate whether the probiotic beverage Yakult 400 (Y400), which contains Lactobacillus casei strain Shirota, improves liver function in ALC patients, and to analyze the precise gut flora profile by real-time quantitative PCR (qPCR).

Segmented filamentous bacteria (SFB) are noncultivable commensals inhabiting the gut of various vertebrate species and have been shown to induce Th17 cells in mice. We present the complete genome sequences of both rat and mouse SFB isolated from SFB-monocolonized hosts. The rat and mouse SFB genomes each harbor a single circular chromosome of 1.52 and 1.59 Mb encoding 1346 and 1420 protein-coding genes, respectively. The overall nucleotide identity between the two genomes is 86%, and the substitution rate was estimated to be similar to that of the free-living E. coli. SFB genomes encode typical genes for anaerobic fermentation and spore and flagella formation, but lack most of the amino acid biosynthesis enzymes, reminiscent of pathogenic Clostridia, exhibiting large dependency on the host. However, SFB lack most of the clostridial virulence-related genes. Comparative analysis with clostridial genomes suggested possible mechanisms for host responses and specific adaptations in the intestine.

Background/Aim: In previous studies, we described the beneficial effects of bifidobacteria-fermented milk in patients with ulcerative colitis (UC). Here, we examined the effects of a live Bifidobacterium breve strain Yakult, a probiotic contained in bifidobacteria-fermented milk, and galacto-oligosaccharide (GOS) as synbiotics in UC patients. Methods: Forty-one patients with mild to moderate UC were assigned to two groups; one group was treated with the synbiotics and the other was not (control). The treatment group ingested 1 g of the probiotic powder (109 CFU/g) three times a day, and 5.5 g of GOS once a day for one year. At the start and the end of this study, colonoscopic index and the amount of myeloperoxidase in a lavage solution were used as disease activity indices. Bacterial counts in the feces at the start and the end of this study were also examined. Results: After a one-year treatment with the synbiotics, the clinical status of the UC patients as assessed by colonoscopy, significantly improved. Furthermore, the amount of myeloperoxidase in the lavage also decreased in these patients after the synbiotic treatment. The synbiotics significantly reduced the fecal counts of Bacteroidaceae and fecal pH. Conclusion: Administration of live B. breve strain Yakult and GOS can improve the clinical condition of patients with UC. These results encouraged us to perform a large-scale randomized, placebo-controlled trial.

Neurogastroenterology & MotilityVolume 22, Issue 10 p. 1148-1148 Role of microbial fermentation products in irritable bowel syndrome S. Fukudo, S. Fukudo Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorY. Umesaki, Y. Umesaki Yakult Central Institute for Microbiological Research, Tokyo, JapanSearch for more papers by this authorA. Imaoka, A. Imaoka Yakult Central Institute for Microbiological Research, Tokyo, JapanSearch for more papers by this authorC. Tana, C. Tana Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorT. Handa, T. Handa Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorM. Kanazawa, M. Kanazawa Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this author S. Fukudo, S. Fukudo Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorY. Umesaki, Y. Umesaki Yakult Central Institute for Microbiological Research, Tokyo, JapanSearch for more papers by this authorA. Imaoka, A. Imaoka Yakult Central Institute for Microbiological Research, Tokyo, JapanSearch for more papers by this authorC. Tana, C. Tana Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorT. Handa, T. Handa Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this authorM. Kanazawa, M. Kanazawa Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanSearch for more papers by this author First published: 02 September 2010 https://doi.org/10.1111/j.1365-2982.2010.01570.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume22, Issue10October 2010Pages 1148-1148 RelatedInformation

Bacteria of the genus Clostridium promote the induction of suppressor T cells in the colons of mice.

Bacteraemia caused by Streptococcus bovis is often associated with colorectal tumours. Also, experimental studies have been proposed that S bovis acts as a promoter of tumours. We report the case of a man with colon adenoma who had a high proportion of S bovis in his faecal flora. He was treated with a Lactobacillus casei preparation (BLP) and the effect on the faecal flora was examined. L casei reduced the proportion of S bovis (from 43% down to 9%), and the effect continued after the administration of BLP was stopped. Our data indicate that BLP can repress the excessive colonisation of S bovis.

G A A b st ra ct s were: “made to have intercourse/oral/anal sex against will” (46.6%), “fondled under force/ threat” (41.8%) and “having seen/handled dead bodies not in a funeral” (40.4%). The TQ also identified high prevalence of traumas (e.g., sex against will because of physical force/ threat (49.4%), sexual harassment (65.1%) and domestic violence (48.2%)), with many reporting occurrence during military service (41.5%, 64.8% and 60.0% respectively). Almost 34% also reported history of childhood sexual abuse. Overall, IBS cases were significantly more likely to experience 9 of 18 THQ traumas, with another 4 closely approaching significance. Excess IBS risk conveyed by selected traumas was modestly increased in ageand ethnicity-adjusted model, with 11 traumas conveying significant risk (OR=1.72 2.43). Women veterans with IBS were also more likely than those without IBS to have PTSD (22.1% vs. 10.7%, p<0.006) and depression (44.2% vs. 30.0%, p=0.01). However, the excess IBS risk was only slightly attenuated after adjusting for these risk factors. ConclusionA high prevalence of IBS, PTSD, and trauma was observed among women veterans. The most commonly reported traumas were sexual, with 49.4% of all women veterans reporting being forced to have sex during their military service. A history of many traumas was associated with an approximately 2-fold increased IBS risk. However, neither PTSD nor depression seems to explain this association.

The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. How commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, 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. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation and antimicrobial defenses and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Thus, manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.

Probiotic foods such as probiotic strain-fermented milk or supplements proposing various health claims are now available. The beneficial effects of these probiotic foods on the digestive system are expected for not only healthy persons but also patients with diseases of the alimentary tract. This review focused on the rationale of using our Bifidobacterium strains-fermented milk as an adjunct for the prevention of recurrence or exacerbation of colitis. Animal experiments using gnotobiotic colitis or spontaneously colitis models and also human clinical trials of ulcerative colitis patients showed the potential of Bifidobacterium strains-fermented milk as a beneficial anti-colitis adjunct.

Background The profile of intestinal organic acids in irritable bowel syndrome (IBS) and its correlation with gastrointestinal (GI) symptoms are not clear. We hypothesized in this study that altered GI microbiota contribute to IBS symptoms through increased levels of organic acids. Methods Subjects were 26 IBS patients and 26 age- and sex-matched controls. Fecal samples were collected for microbiota analysis using quantitative real-time polymerase chain reaction and culture methods, and the determination of organic acid levels using high-performance liquid chromatography. Abdominal gas was quantified by image analyses of abdominal X-ray films. Subjects completed a questionnaire for GI symptoms, quality of life (QOL) and negative emotion. Key Results Irritable bowel syndrome patients showed significantly higher counts of Veillonella (P = 0.046) and Lactobacillus (P = 0.031) than controls. They also expressed significantly higher levels of acetic acid (P = 0.049), propionic acid (P = 0.025) and total organic acids (P = 0.014) than controls. The quantity of bowel gas was not significantly different between controls and IBS patients. Finally, IBS patients with high acetic acid or propionic acid levels presented with significantly worse GI symptoms, QOL and negative emotions than those with low acetic acid or propionic acid levels or controls. Conclusions & Inferences These results support the hypothesis that both fecal microbiota and organic acids are altered in IBS patients. A combination of Veillonella and Lactobacillus is known to produce acetic and propionic acid. High levels of acetic and propionic acid may associate with abdominal symptoms, impaired QOL and negative emotions in IBS.

AIM To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted. RESULTS Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-alpha, whereas no such effect was observed with heat-killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IkappaB-zeta mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM. CONCLUSION Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.

Probiotics are used for the improvement of gut disorders. To explore the potential of probiotics, a gnotobiotic study using BALB/c mice to analyze epithelial gene expression was performed. Microarray analysis of probiotic strain-monoassociated mice showed that Lactobacillus casei Shirota and Bifidobacterium breve Yakult noticeably affected gene expression in the ileal and colonic epithelial cells, respectively, although to a smaller extent than segmented filamentous bacteria (SFB). Lactobacillus casei Shirota enhanced the gene expression involving defense/immune functions and lipid metabolism more strongly than B. breve Yakult. In the colon, expression of a chloride transporter was slightly enhanced, although downregulation of many genes, such as guanine nucleotide-binding protein, was evident in mice with B. breve Yakult compared with the ones with L. casei Shirota. SFB affected gene expression more strongly than the probiotic strains. In particular, alpha(1-2) fucosyltransferase and pancreatitis-associated protein were significantly enhanced only in SFB-monoassociated mice but not probiotic strain-monoassociated mice. Gene expression of SFB-monoassociated mice was either stimulated or repressed in a manner similar to or opposite that of conventional colonized mice. Taken together, probiotic strains of L. casei Shirota and B. breve Yakult differentially affect epithelial gene expression in the small intestine and colon, respectively.

Aims: Animal models are required for evaluation of the functional foods such as pro/prebiotics exerting effects through the metabolism of the intestinal microflora. The object of this study was to establish new human flora-associated mice reflecting the environment of the human intestinal tract.Methods and Results: We inoculated a human faecal suspension into segmented filamentous bacteria (SFB) monoassociated mice as a model system. In both human flora (HF) and SFB-associated mouse (HF-SFB mouse), intestinal characteristics such as the composition of intraepithelial lymphocytes, the expression of major histocompatibility complex (MHC) class II molecules and the number of immunoglobulin A-producing cells in the mucosa was closer to those of conventionally reared mice than was case with human flora-associated mice (HF mice) lacking SFB. Several predominant bacterial groups except lactobacilli in human flora were found in faeces of HF-SFB mice. Lactobacilli established small populations in the gut of HF-SFB mice when administered before inoculation with the human flora. Faecal enzymatic activities and organic acid concentration of HF-SFB mice proportionally reflected those of the donor subject.Conclusion: We established a new human flora-associated mouse (HF-SFB mouse), in which intestinal characteristics are normally developed and their major microbial composition reflect the human.Significance and Impact of the Study: HF-SFB mice are a valuable model for studying pro/prebiotic effects on the human intestine.

BACKGROUND:Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.AIM:To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis.METHODS:Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment.RESULTS:Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group.CONCLUSION:Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.

Indigenous Bacteroides strains are closely associated with the occurrence and exacerbation of ulcerative colitis (UC). In this study, we aimed to clarify the effect of Bifidobacterium strains, another major member of colonic bacteria, on the development of gut inflammation using gnotobiotic mouse models associated with Bacteroides strains isolated from UC patients. Dextran sulfate (DSS) administration induced inflammation in the large intestine, in particular of the cecum, in the gnotobiotic mice associated with three strains of Bacteroides vulgatus, judging from the myeloperoxidase activity, occult blood score, and IgG leakage into the intestinal contents. However, the severity of the inflammation was greatly reduced in the gnotobiotic mice associated with both B. vulgatus and Bifidobacterium strains. The severity of the cecal inflammation was well correlated with the concentration of succinic acid in the cecum. Bacteriologically, the density of B. vulgatus strain A (BV-A) greatly decreased and the predominant strain changed from BV-A to BV-B on additional association with Bifidobacterium strains. Among gnotobiotic mice associated with a single B. vulgatus strain, the severity of cecal inflammation in BV-A-associated mice was greater than that in BV-B-associated mice. Each Bifidobacterium strain produced compound(s) more effectively inhibiting the growth of BV-A than BV-B in in vitro culture. Taken together, these results suggest that the severity of DSS-induced gut inflammation is closely associated with a particular B. vulgatus strain, and that Bifidobacterium strains may repress exacerbation of intestinal inflammation through growth inhibition of the B. vulgatus strain.

Background: Alterations of intestinal flora, such as reduction in the concentration of bifidobacteria and increase in that of Bacteroides species, are apparently associated with the severity of ulcerative colitis.Objective: We conducted a randomised clinical trial of the use of a bifidobacteria-fermented milk (BFM) supplement as a dietary adjunct in the treatment of ulcerative colitis.Methods: The subjects were randomly divided into two groups: a group with BFM supplementation (BFM group, 11 subjects) and a control group (control group, 10 subjects). The BFM group was given 100 mL/day of BFM for one year. Colonoscopies, general blood markers and examinations of intestinal flora including the analysis of fecal organic acids were performed at the commencement of the study and after one year.Results: Exacerbation of symptoms was seen in 3 out of 11 subjects in the BFM group and in 9 out of 10 in the control group. Log rank statistic analysis of the cumulative exacerbation rates showed a significant reduction in exacerbations for the BFM group (p = 0.0184). The analysis of microflora and the organic acids in the feces showed a significant reduction in the relative proportion of B. vulgatus in Bacteroidaceae and butyrate concentration, respectively, after supplementation with BFM, in comparison with before.Conclusion: Supplementation with the BFM product was successful in maintaining remission and had possible preventive effects on the relapse of ulcerative colitis.