Enhancing butyrate synthesis and intestinal epithelial energy supply through mixed probiotic intervention in dextran sulfate sodium-induced colitis

Inflammatory bowel disease (IBD) is a globally prevalent gastrointestinal disorder that considerably impairs life quality. Probiotics are considered potential therapeutic agents for IBD because of their multifaceted effects. In this study, we evaluated the therapeutic effects of a mixture of probiotics ( Lactobacillus rhamnosus , Lactobacillus plantarum , and Clostridium butyricum ) on dextran sulfate sodium (DSS)-induced colitis in mice. To determine its anti-inflammatory mechanism, we employed metagenomic sequencing to analyze the effects of mixed probiotics on butyrate-producing bacteria and related genes in the gut. Immunofluorescence, immunohistochemistry, and flow cytometry were used to detect the effects of mixed probiotics on the intestinal barrier, immune function, and mitochondrial function in mice. Finally, in vitro fermentation experiments were conducted to evaluate the anti-inflammatory effects of the intestinal flora in mice relative to antibiotics. Our findings demonstrated that mixed probiotics enhance the conversion of lactate to butyrate by restoring the acetyl-CoA pathway in the colonic microbiota of mice with DSS-induced colitis. This restoration, in turn, led to the restoration of butyrate levels in the intestine and the activation of the butyrate receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) to sustain the energy supply of intestinal epithelial cells. Consequently, this intervention reinforced the intestinal barrier integrity and modulated intestinal immune responses. In conclusion, mixed probiotics alleviate colitis, providing a potential therapeutic strategy for IBD.