Chondroitin sulfate stimulates the secretion of H2S by Desulfovibrio to improve insulin sensitivity in NAFLD mice.

Hydrogen sulfide (H2S) is a bioactive gas regulating insulin secretion and sensitivity, produced by sulfate-reducing bacteria in the gut. The present study investigated the effect of chondroitin sulfate (CS) treatment, which indirectly increased the H2S production on nonalcoholic fatty liver disease (NAFLD). A 7-week CS supplementation had beneficial effects on body weight gain, liver function, hepatic histology, and serum lipid levels. CS could ameliorate diet-induced insulin resistance and improve insulin sensitivity via the AKT pathway, and modulate gut microbiota composition, especially increased the abundance of Desulfovibrio and elevated levels of hydrogen sulfide (H2S). Collectively, these findings suggested that CS treatment was positively correlated with Desulfovibrio in the gut, and the metabolic H2S flowed into the liver via the gut-liver axis, thereby triggering the AKT signaling pathway and improving insulin resistance. Thus, CS-induced alterations in the gut microbiota seem a promising for ameliorating NAFLD.