Commensal Lactobacillus stimulates the intestinal methionine metabolism of weaning piglets by reshaping gut microbiota and metabolites

Abstract Background The mammalian gastrointestinal tract hosts a complex microbiome essential for sustaining host health, particularly during pivotal stages such as weaning in piglets. Weaning represents a significant stressor, leading to substantial shifts in the gut microbiota composition and functionality. This study investigated the impact of weaning stress on the gut microbiome and metabolite profiles of piglets, focusing on how methionine supplementation influences gut health and physiological development. Results A multiomics approach that integrates metagenomics, metabolomics, culturomics, and transcriptomics was employed to characterize the gut microbiota before and after weaning. During the weaning period, weaning stress was characterized by a reduction in the abundance of beneficial bacteria in the gut, particularly a significant decrease in commensal Lactobacillus species, such as L. mucosae , L. reuteri , and L. amylovorus . Metabolomic analysis further revealed reductions in methionine and other metabolites associated with methionine metabolism and reductions in branched-chain amino acids (BCAAs) and lipid-related metabolites. Analysis of culture supernatants from Lactobacillus isolates demonstrated that these commensal Lactobacillus produced methionine, methionine-related metabolites, and BCAAs, highlighting a close relationship between methionine and commensal Lactobacillus abundance under weaning stress. Moreover, methionine supplementation in intestinal epithelial cells under methionine-deficient conditions led to the upregulation of genes related to methionine and pyruvate metabolism. Conclusions Weaning stress results in the simultaneous reduction of both commensal Lactobacillus abundance and methionine levels in the piglet gut, with a significant inter-relationship between these factors. Methionine supplementation shows potential in mitigating gut dysbiosis and metabolic disruptions induced by weaning stress. Graphical abstract