Dietary methionine restriction restores wheat gluten-induced celiac-associated small intestine damage in association with affecting butyric acid production by intestinal flora.

Methionine restriction has received some attention in recent years as a novel mode of dietary intervention. Our previous study found that methionine restriction could inhibit the celiac toxic effects of wheat gluten in an in vitro model. However, the role of methionine restriction in gluten-induced celiac intestinal damage remains unclear. The aim of this study was to explore whether dietary methionine restriction could suppress the celiac toxic effects of gluten in an in vivo model, thereby mitigating intestine damage. This study systematically investigated the effects of dietary methionine restriction on celiac characteristic indicators such as symptoms, small intestine damage, and intestinal TG2 and IL-15 expression in a gluten-induced C57BL/6 mouse model. The availability of dietary methionine restriction in different ages (adolescent and adult) was also evaluated. Moreover, mouse cecum contents were assayed and co-analyzed for the metagenome of intestinal flora and target short-chain fatty acid metabolomics, with the goal of further exploring and elucidating critical pathways by which dietary methionine restriction plays a role. We discovered that dietary methionine restriction could effectively ameliorate the gluten-induced celiac-associated small intestine damage by modulating intestinal flora to inhibit butyric acid production. Specifically, dietary methionine restriction could inhibit butyric acid production with the help of s_CAG-485 sp002493045 and s_CAG-475 sp910577815, which in turn affected the mitochondrial function within the intestinal epithelial cells to assist in the repair of intestine damage. This study might provide new insights into modulating dietary patterns to mitigate intestinal damage in celiac disease and the production of novel gluten-free products.