Wheat Bran Arabinoxylan Potentiates Hepatoprotective Efficacy of Postbiotic <i>Limosilactobacillus reuteri</i> in Colitis Mice via a Gut–Liver Axis

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 <i>Limosilactobacillus reuteri</i> WX-94, enhancing its tryptophan metabolism to produce indole-3-acetic and indole-lactic acids <i>in vitro</i>. Oral administration of WBAX-<i>L. reuteri</i> postbiotic alleviated colitis and hepatic disorders, outperforming strains cultured with glucose- or xylo-oligosaccharide. Multiomics analysis showed that WBAX-<i>L. reuteri</i> restored metabolic homeostasis and activated hepatic FXR/SHP/PPAR signaling, improving bile acid and lipid metabolism. Key microbial contributors included <i>Faecalibacterium</i>, Burkholderiales, Christensenellaceae_R-7_group, <i>Muribaculum</i>. Mendelian randomization suggested causal relationship between WBAX-<i>L. reuteri</i>-enhanced bacteria and bile-acid-metabolizing enzymes, while molecular docking confirmed bile acid-protein interactions. Additionally, WBAX-<i>L. reuteri</i>'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 <i>L. reuteri</i>, offering postbiotic strategies for improving colon health and associated metabolic functions via a gut-liver axis.