Alpha-lipoic acid improves intestinal homeostasis and ameliorates colitis through modulation of gut microbiota and production of short chain fatty acids in mice.

Abstract

α-Lipoic acid (ALA) is a natural antioxidant present in both plants and animal foods. It has attracted growing attention for its potential role in maintenance of intestinal homeostasis. This study was to investigate the protective effects of dietary ALA on experimental colitis, and to evaluate its modulating effect on gut microbiome in mice. Male C57BL/6 J mice with dextran sulfate sodium (DSS)-induced acute colitis were administered ALA (40 or 80 mg/kg) dissolved in corn oil. Results showed that dietary ALA ameliorated colitis severity, improved intestinal barrier integrity, and attenuated inflammation by reducing oxidative stress and suppressing NF-κB pathway activation and pro-inflammatory cytokines expression. Moreover, dietary ALA increased the microbial diversity (Shannon index), reshaped gut microbiota composition by suppressing pathogenic bacteria and promoting beneficial taxa such as Akkermansia, and elevated levels of short chain fatty acids (SCFA). Fecal microbiota transplantation (FMT) further confirmed that ALA could modulate gut microbiota and protect against colitis in mice. In conclusion, ALA could effectively maintain the intestinal homeostasis and ameliorate colitis at least in mice. Such protective effect of ALA in gut health was mediated through modulation of gut microbiota and enhancement of SCFA production.