2'-Fucosyllactose enhances indole-3-lactic acid production by Bifidobacterium bifidum DNG-08 and alleviates colitis-associated bone loss: Associations with microbiota remodeling and intestinal AHR-related responses.

Inflammatory bowel disease is frequently associated with an imbalance in bone remodeling and a decline in bone mass, however, there is a lack of systematic research on microbiome-based intervention strategies targeting colitis-associated bone loss. In this study, Bifidobacterium bifidum DNG-08 (DNG-08) was selected from four candidate strains based on its favorable 2'-fucosyllactose (2'-FL) utilization and indole-3-lactic acid (ILA) production. Genomic annotation revealed that DNG-08 harbors functional genes related to fucosylated oligosaccharide utilization and the conversion of tryptophan to ILA. In a dextran sulfate sodium (DSS)-induced mouse model, combined intervention with DNG-08 and 2'-FL significantly alleviated colitis-associated phenotypes, and reduced pro-inflammatory cytokine levels by 13.33%-58.69%, while increasing IL-10-1.23 times that of the DSS group. Simultaneously, the combined intervention improved trabecular bone microstructure, increasing the bone formation marker procollagen type I N-terminal propeptide (PINP) by 14.61%-56.37%, decreasing the bone resorption marker C-terminal telopeptide of type I collagen (CTX-I) by 17.03%-21.77%, and upregulating the expression of Wnt3a, β-catenin, and Runx2. Gut microbiota analysis showed that combined intervention could partially reverse DSS-induced dysbiosis, enriching potentially beneficial bacterial taxa while reducing inflammation-associated genera. Notably, combined treatment group exhibited elevated serum ILA levels, increased colonic aryl hydrocarbon receptor (AHR) fluorescence, and upregulatied CYP1A1 expression. Correlation analysis identified significant associations among serum ILA, AHR-related indicators, selected bacterial genera, and bone remodeling parameters. This study highlights that strain-substrate matching may serve as a precise synbiotic strategy to improve inflammation-related gut-bone axis dysfunction.