Abstract

Postbiotics demonstrate superior stability and safety compared to probiotics. We found that wheat bran arabinoxylan (WBAX) served as an effective substrate for the tryptophan-metabolizing probiotic Limosilactobacillus reuteri WX-94, enhancing its tryptophan metabolism to produce indole-3-acetic and indole-lactic acids in vitro. Oral administration of WBAX–L. reuteri postbiotic alleviated colitis and hepatic disorders, outperforming strains cultured with glucose- or xylo-oligosaccharide. Multiomics analysis showed that WBAX–L. reuteri restored metabolic homeostasis and activated hepatic FXR/SHP/PPAR signaling, improving bile acid and lipid metabolism. Key microbial contributors included Faecalibacterium, Burkholderiales, Christensenellaceae_R-7_group, Muribaculum. Mendelian randomization suggested causal relationship between WBAX–L. reuteri-enhanced bacteria and bile-acid-metabolizing enzymes, while molecular docking confirmed bile acid–protein interactions. Additionally, WBAX–L. reuteri’s lipid-modulating effects were confirmed in HepG2 cells within the safe toxicity range. Our findings highlight WBAX’s role in enhancing therapeutic potential of postbiotic L. reuteri, offering postbiotic strategies for improving colon health and associated metabolic functions via a gut–liver axis.