Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis

Abstract

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-α 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-α (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.

Keywords:

• Microbiota
• colitis
• oncostatin M
• tight junction
• anti-TNF therapy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (81670504 and 81472287) and by the Natural Science Foundation Youth Project of Hunan Province (2017JJ3468).