Mucin-mimetic action of capsaicin improves high fat diet-induced gut barrier dysfunction in mice colon

Abstract

The gut barrier - including tight junction proteins and mucus layers, is the first line of defense against physical, chemical, or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While its mode of action is well established to enhance energy expenditure, metabolism and prevent dysbiosis, the more local effects on the host gut - particularly the gut barrier and mucus system remain elusive. We employed a diet-induced obesity model to investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena. Mucin feeding reflected most of the effects produced by capsaicin, indicating that mucus modulation by capsaicin plays a crucial role in its anti-obesity effects. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment. HIGHLIGHTSO_LIExogenous mucin feeding produced anti-obesity effects similar to capsaicin in mice. C_LIO_LIMucin and capsaicin improved TJP expression, intestinal permeability and gut microbial diversity. C_LIO_LICapsaicin modulated bacterial diversity in vitro, independently of the host. C_LIO_LIProbiotic bacteria and butyrate activated TRPV1 in transfected HEK cells. C_LIO_LIAnti-obesity action of capsaicin is not exclusive to TRPV1 agonism. C_LIO_LICapsaicins action as colonic mucus secretagogue - plays a crucial part in its anti-obesity benefits. C_LI