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Bifidobacterium longum alleviates irritable bowel syndrome-related visceral hypersensitivity and microbiota dysbiosis via Paneth cell regulation.

ABSTRACT: Although the oral administration of Bifidobacterium longum (B. longum) relieves the signs of irritable bowel syndrome (IBS) in clinical settings, the mechanisms underlying its effects are unclear. In this study, we evaluated the precise effects of B. longum on IBS via regulation of Paneth cell function. We confirmed the beneficial effects of B. longum on defecation habits and visceral hypersensitivity in WAS rats. Further analysis revealed that B. longum enhanced mucosal repair, promoted lysozyme production, and ameliorated dysbiosis of the microbiota in WAS rats. These processes are closely correlated with Paneth cell functions. In vitro, we incubated primary cultured enteroids with B. longum and found that B. longum promoted the proliferation of these organoids; this may be attributed to the upregulation of the stem niche factors WNT3A and TGF-β, which are secreted by Paneth cells. Based on our findings, we propose that B. longum relieves IBS by restoring the antimicrobial activity and stem niche maintenance function of Paneth cells.

SUBMITTER: Zhou C

PROVIDER: S-EPMC7524277 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Bifidobacterium longum alleviates irritable bowel syndrome-related visceral hypersensitivity and microbiota dysbiosis via Paneth cell regulation.

Zhou Chunhua C Fang Xue X Xu Jiajia J Gao Jun J Zhang Ling L Zhao Jiulong J Meng Yuting Y Zhou Wei W Han Xu X Bai Yu Y Li Zhaoshen Z Zou Duowu D

Gut microbes 20200625 1

Although the oral administration of Bifidobacterium longum (B. longum) relieves the signs of irritable bowel syndrome (IBS) in clinical settings, the mechanisms underlying its effects are unclear. In this study, we evaluated the precise effects of B. longum on IBS via regulation of Paneth cell function. We confirmed the beneficial effects of B. longum on defecation habits and visceral hypersensitivity in WAS rats. Further analysis revealed that B. longum enhanc ...[more]

PMID: 32584650

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Project description:BackgroundBifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome (IBS) symptoms compared with placebo in double-blind randomized studies. However, few data are available from real-life clinical practice or from studies that used Rome IV criteria to diagnose IBS.AimTo assess the effect of B. longum 35624 on IBS severity and quality of life in a real-life setting.MethodsFrom November 2018 to January 2020, 278 patients with IBS (according to Rome IV criteria) were enrolled in a prospective, open-label, multicenter observational study by private practice gastroenterologists to received one capsule of B. longum 35624 (109 colony-forming units) per day for 30 d. Participation in the study was independently proposed to patients during spontaneous consultations. Disease severity (assessed by the IBS severity scoring system) and patient quality of life (assessed by the IBS quality of life questionnaire) were compared between the inclusion visit (baseline) and the visit at the end of 30 d of treatment. The characteristics of patients were described at baseline. Continuous variables comparisons between inclusion and end-of-treatment visits were performed using the t-test and Kruskal-Wallis test. Categorical variables comparisons were performed using the χ2 test.ResultsA total of 233 patients, with a mean age of 51.4 years and composed of 71.2% women, were included in the study. Of these patients, 48.1% had moderate IBS and 46.4% had severe IBS. After a 30-d treatment period with one B. longum 35624 capsule per day, a significant decrease in IBS severity was observed compared to baseline (mean ± SD, IBS severity scoring system scores: 208 ± 104 vs 303 ± 81, P < 0.001) and 57% of patients moved to lower severity categories or achieved remission. The quality of life of patients was also improved by the treatment (IBS Quality of Life questionnaire score: 68.8 ± 20.9 vs 60.2 ± 20.5; P < 0.001) and 63.8% of patients were satisfied with the treatment.ConclusionThirty days of treatment with B. longum 35624 reduces disease severity and improves the quality of life of patients with IBS, particularly those with the most severe forms of IBS.

Project description:Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity (VH) associated with abnormal serotonin/5-hydroxytryptamine (5-HT) metabolism and neurotrophin-dependent mucosal neurite outgrowth. The underlying mechanisms of VH remain poorly understood. We investigated the role of 5-HT7 receptor in mucosal innervation and intestinal hyperalgesia. A high density of mucosal nerve fibres stained for 5-HT7 was observed in colonoscopic biopsy specimens from IBS patients compared with those from healthy controls. Staining of 5-HT3 and 5-HT4 receptors was observed mainly in colonic epithelia with comparable levels between IBS and controls. Visceromotor responses to colorectal distension were evaluated in two mouse models, one postinfectious with Giardia and subjected to water avoidance stress (GW) and the other postinflammatory with trinitrobenzene sulfonic acid-induced colitis (PT). Increased VH was associated with higher mucosal density of 5-HT7-expressing nerve fibres and elevated neurotrophin and neurotrophin receptor levels in the GW and PT mice. The increased VH was inhibited by intraperitoneal injection of SB-269970 (a selective 5-HT7 antagonist). Peroral multiple doses of CYY1005 (a novel 5-HT7 ligand) decreased VH and reduced mucosal density of 5-HT7-expressing nerve fibres in mouse colon. Human neuroblastoma SH-SY5Y cells incubated with bacteria-free mouse colonic supernatant, 5-HT, nerve growth factor, or brain-derived neurotrophic factor exhibited nerve fibre elongation, which was inhibited by 5-HT7 antagonists. Gene silencing of HTR7 also reduced the nerve fibre length. Activation of 5-HT7 upregulated NGF and BDNF gene expression, while stimulation with neurotrophins increased the levels of tryptophan hydroxylase 2 and 5-HT7 in neurons. A positive-feedback loop was observed between serotonin and neurotrophin pathways via 5-HT7 activation to aggravate fibre elongation, whereby 5-HT3 and 5-HT4 had no roles. In conclusion, 5-HT7-dependent mucosal neurite outgrowth contributed to VH. A novel 5-HT7 antagonist could be used as peroral analgesics for IBS-related pain.

Project description:Objective: To investigate the effect of Massa Medicata Fermentata (MMF) on the changes of pathogenic flagellar bacteria and visceral hypersensitivity in rats with diarrhea irritable bowel syndrome (IBS-D). Methods: Thirty adult SD rats were randomly divided into normal control group (n = 10), model control group (n = 10), and MMF group (n = 10). Acetic acid enema combined with restraint stress was used to build the IBS-D visceral hypersensitivity model; Abdominal withdrawal reflex (AWR) test was used to assess the visceral sensitivity of rats; 16SrRNA sequencing was used to analyze the changes of intestinal bacteria in each group, and the content of pathogenic flagellated bacteria were quantitatively counted; The content of flagellin in colonic mucosa was detected by ELISA; TLR5 protein in colonic mucosa of rats was detected by Western Blot. Results: After IBS-D modeling, the visceral sensitivity of rats was significantly higher in the model control group than that in the normal control group (p = 0.0061), while it was significantly decreased in MMF group compared with the model control group (p = 0.0217), but without significant difference compared with the normal control group (p = 0.6851). The number of fecal Bifidobacterium and Lactobacillus in the model group were significantly decreased compared with the normal control group (p < 0.0001); While they were significantly increased in the MMF group compared with the model control group and normal control group (p = 0.009; p < 0.0001). The amount of fecal pathogenic flagellated bacteria in the model group was significantly increased compared with the normal control group (p = 0.001); However it was significantly reduced in MMF group compared with the model group (p = 0.026), which has no statistically difference with the normal control group (p = 0.6486). The content of flagellin in colonic mucosa was significantly increased in the model group when compared with the normal control group (p < 0.0001), and it was decreased in MMF group compared with the normal control group (p < 0.0001), but there was no statistical difference with the normal control group (p = 0.6545). The expression level of TLR5 protein in colonic mucosa of rat was significantly increased in model control group compared with the normal control group (p = 0.0034), However, it was significantly decreased in MMF group compared with normal control group (p = 0.0019), but it was no statistical difference with the normal control group (p = 0.7519). Conclusion: MMF can reduce visceral hypersensitivity by decreasing the content of pathogenic flagellated bacteria and their flagellin and inhibiting its specific receptor TLR5 protein expression in colonic mucosa in IBS-D rats.

Dataset Information

Bifidobacterium longum alleviates irritable bowel syndrome-related visceral hypersensitivity and microbiota dysbiosis via Paneth cell regulation.

Publications

<i>Bifidobacterium longum</i> alleviates irritable bowel syndrome-related visceral hypersensitivity and microbiota dysbiosis via Paneth cell regulation.

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