Heat stress-induced intestinal barrier damage and dimethylglycine alleviates via improving the metabolism function of microbiota gut brain axis

Heat stress, a widely occurred in subtropical climate regions, causes ecosystem destruction, and intestine injury in humans and animals. As an important compound in the metabolic pathway of choline, dimethylglycine (DMG) shows anti-inflammatory effects. This study examines the beneficial effects of dietary DMG against heat stress -induced intestine injury and further explores the underlying molecular mechanisms using a broiler model. Here, we showed that DMG supplements exhibited positive effects to growth performance, as evidenced by the significantly increased body weight and feed conversion rate. These therapeutic effects attributed to repaired gut barrier integrity, increased content of anti-inflammatory cytokines IL-10, decreased content of pro-inflammatory cytokines IL-6, and down-regulated gene expression of the NF-kappa B signaling pathway. DMG treatment led to the reshaping of the gut microbiota composition, mainly increasing the short-chain fatty acid (SCFAs) strains such as Faecalibacterium, and Marvinbryantia. DMG treatment also increased two main members of SCFAs, including acetate acid and isobutyrate. Particularly, distinct effects were found which mediated the tryptophan metabolism in intestines such as increased tryptophan and 5-HT, which further alleviate the occurrence of intestinal barrier damage caused by heat stress. Additionally, DMG treatment promoted neuroendocrine function and stimulated the hypothalamic neurotransmitter metabolism by activating tryptophan metabolism in the hypothalamus. Overall, DMG supplementation effectively reduced the occurrence of intestinal inflammation induced by heat stress through modulating cecal microbial communities and improving the metabolism function of microbiota gut brain axis. Our findings revealed a novel mechanism by which gut microbiota could improve host health.