Dietary methionine restriction ameliorates ulcerative colitis in mice: A role for the H₂S and short-chain fatty acids balance via gut microbiota remodeling.

Dietary methionine restriction (MR) has been shown to alleviate ulcerative colitis (UC), while the optimal degree of restriction and the mechanisms involved remain unclear. This study aims to investigate the effects of different levels of MR intervention on dextran sulfate sodium (DSS)-induced UC and the underlying mechanisms. The mice were randomly assigned to six groups: CON (0.86% methionine, normal water) and different levels of MR intervention (0.86%, 0.69%, 0.52%, 0.34%, and 0.17% methionine, 3% DSS). The results show that different levels of MR intervention increased colon length, reduced body weight change and disease activity index score, and improved colon tissue damage. In addition, the intervention upregulated anti-inflammatory cytokine levels, downregulated pro-inflammatory cytokine levels, and improved oxidative stress in colon. Moreover, the intervention increased colon and plasma immunoglobulin levels, promoted the expression of colonic tight junction proteins and mucins, improved intestinal barrier function, and lowered intestinal permeability. Furthermore, MR at various levels lowered the abundance of H2S-producing bacteria, raised the abundance of short-chain fatty acid (SCFA)-producing bacteria, and improved gut microbiota composition. Additionally, the intervention altered enteral H2S and SCFA production pathways, decreased H2S levels, and increased SCFA levels in colon. The aforementioned beneficial effects increase initially and then decrease with the intervention dosage, with the 40% MR dosage (0.52% methionine in diet) showing the best improvement. Thus, MR ameliorates UC, and the underlying mechanism may be associated with balancing the levels of H₂S and SCFAs via gut microbiota remodeling. A 40% MR diet is recommended for improving pathological conditions in UC patients.