(R)-Bambuterol attenuates DSS-induced chronic colitis by suppressing inflammation, repairing intestinal barrier, and modulating gut microbiota and serum metabolomic profile.

Ulcerative colitis (UC) is a chronic and recurrent intestinal inflammatory disease, owing to its increasing incidence worldwide, UC poses a serious threat to human health. Existing treatments do not meet the needs of patients. (R)-Bambuterol ((R)-BMB) is a β2 receptor agonist that is mainly used for the treatment of respiratory diseases. Previous studies had reported that (R)-BMB owned immunomodulatory effect, but its effect on chronic intestinal inflammation has not yet been evaluated. In the present study, we investigated the potential effects and mechanisms of (R)-BMB in mice with dextran sodium sulfate (DSS)-induced chronic colitis. The symptoms of chronic colitis, such as weight loss, colon shortening, and bloody stools, were attenuated via treatment with (R)-BMB. Pathological analysis of colon tissue revealed that (R)-BMB mitigated colon tissue damage in mice with chronic colitis. Besides, (R)-BMB suppressed M1 macrophage polarization and reduced the level of inflammatory cytokines. In addition, treatment with (R)-BMB elevated the expression of the tight junction proteins zonula occludens-1 (ZO-1) and Occludin and prevented the expression of the transforming growth factor-β1 (TGF-β1) and alpha smooth muscle actin (α-SMA) intestinal fibrosis markers. Furthermore, 16S rDNA amplicon sequencing revealed that (R)-BMB restored the homeostasis of the intestinal microbiota, and untargeted metabolomics analysis revealed that the changes in the metabolomics profiles were restored after (R)-BMB treatment. In conclusion, (R)-BMB alleviated the mice with DSS-induced chronic colitis via inhibiting the immune response and reshaping the intestinal microbiota and metabolic profiles, which provides a preclinical foundation for future development of novel therapeutics for chronic colitis.