(R)-bambuterol ameliorates DSS-induced colitis in mice fed a high-fat diet via modulating immune response, intestinal barrier integrity, gut microbiota, and metabolomic profiles

Abstract

The consumption of a high-fat diet is currently thought to be closely related to the onset of ulcerative colitis. (R)-bambuterol ((R)-BMB) has anti-inflammatory effects in the treatment of respiratory system related diseases. However, the therapeutic effect of (R)-BMB against in high-fat diet-related colitis remain undocumented. Therefore, in this study, the alleviation effect of (R)-BMB in mice with dextran sulfate sodium (DSS)-induced colitis fed a high-fat diet and its potential mechanism was explored. The results demonstrated that (R)-BMB markedly ameliorated the symptoms of colitis, such as body weight loss, spleen swelling and colon shortening. Moreover, (R)-BMB obviously mitigated the levels of inflammatory cytokines. Further research exhibited that (R)-BMB inhibited the NF-κB signaling pathway, regulated the balance of Th17 and Treg cells, elevated activated the Nrf-2/HO-1 signaling pathway, and increased the expression of related to tight junction proteins to increase the integrity of the intestinal barrier. In addition, 16S rDNA sequencing results indicated that (R)-BMB regulated the structure of the intestinal microbiome and relieved imbalances in this microbiome, and non-targeted metabolomics analysis revealed that (R)-BMB reversed the metabolic changes in mice with colitis fed a high-fat diet. In summary, these results indicate that (R)-BMB can serve as a novel alternative strategy for treating colitis in the context of high-fat diet consumption.