PMID- 30946611 OWN - NLM STAT- MEDLINE DCOM- 20200501 LR - 20200501 IS - 1502-7708 (Electronic) IS - 0036-5521 (Linking) VI - 54 IP - 4 DP - 2019 Apr TI - Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis. PG - 432-440 LID - 10.1080/00365521.2019.1595708 [doi] AB - Objective: Levels of oncostatin M (OSM) and the composition of gut microbiota predict responses to anti-TNF agents used for IBD therapy. Here, the aim was to investigate the effects of Roseburia intestinalis, a gut microbiota, on OSM and on intestinal barrier in colitis. Methods: In the murine model of 3% dextran sulfate sodium (DSS)-induced colitis, we tested disease activity index (DAI), colon length, histological score and expression of tight junction (TJ) proteins (ZO-1, occludin and claudin-1), OSM, TNF-alpha and TLR5. In addition, a cellular model was used to examine the role of R. intestinalis during secretion of OSM by lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and TLR5 knockout (TLR5 KO) mice. Furthermore, we evaluated the impact of OSM on expressions of TJ proteins by Caco-2 cells. Results: R. intestinalis in DSS-induced colitis decreased DAI score (p < .001), colon length shortening (6.46 +/- 0.36 cm vs 5.65 +/- 0.47 cm, p = .022), histological score (2.667 +/- 1.15 vs 5.33 +/- 1.14, p = .018) and increased expression of TJ proteins (p < .05). In addition, R. intestinalis reduced expression of OSM (p < .05) and TNF-alpha (p < .05), while increasing expression of TLR5 (p < .05). Furthermore, R. intestinalis reduced secretion of OSM (p < .05) by LPS-induced BMDMs isolated from WT and TLR5 KO mice. Moreover, OSM downregulated expression of TJ proteins (p < .05) by Caco-2 cells in a concentration-dependent manner. Conclusions: These results indicate that R. intestinalis attenuates inflammation in IBD by decreasing secretion of OSM and by promoting intestinal barrier function. Taken together, the data provide insight into the role of the gut microbiota in patients with IBD who are resistant to anti-TNF therapy. FAU - Tan, Bei AU - Tan B AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Luo, Weiwei AU - Luo W AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Shen, Zhaohua AU - Shen Z AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Xiao, Mengwei AU - Xiao M AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Wu, Shuai AU - Wu S AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Meng, Xiangrui AU - Meng X AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Wu, Xing AU - Wu X AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Yang, Zhenyu AU - Yang Z AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Tian, Li AU - Tian L AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. FAU - Wang, Xiaoyan AU - Wang X AD - a Department of Gastroenterology , Third Xiangya Hospital, Central South University , Changsha , China. AD - b Hunan Key Laboratory of Nonresolving Inflammation and Cancer , Changsha , China. LA - eng PT - Journal Article DEP - 20190404 PL - England TA - Scand J Gastroenterol JT - Scandinavian journal of gastroenterology JID - 0060105 RN - 0 (Tlr5 protein, mouse) RN - 0 (Toll-Like Receptor 5) RN - 0 (Tumor Necrosis Factor-alpha) RN - 106956-32-5 (Oncostatin M) RN - 9042-14-2 (Dextran Sulfate) RN - Roseburia intestinalis SB - IM MH - Animals MH - Caco-2 Cells MH - Clostridiales/*physiology MH - Colitis/*metabolism/microbiology MH - Colon/pathology MH - Dextran Sulfate MH - Disease Models, Animal MH - Female MH - Humans MH - Intestinal Mucosa/microbiology/*pathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Oncostatin M/*metabolism MH - Tight Junctions/*metabolism MH - Toll-Like Receptor 5/genetics MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Microbiota OT - anti-TNF therapy OT - colitis OT - oncostatin M OT - tight junction EDAT- 2019/04/05 06:00 MHDA- 2020/05/02 06:00 CRDT- 2019/04/05 06:00 PHST- 2019/04/05 06:00 [pubmed] PHST- 2020/05/02 06:00 [medline] PHST- 2019/04/05 06:00 [entrez] AID - 10.1080/00365521.2019.1595708 [doi] PST - ppublish SO - Scand J Gastroenterol. 2019 Apr;54(4):432-440. doi: 10.1080/00365521.2019.1595708. Epub 2019 Apr 4.