Bletilla striata oligosaccharides alleviate high-fat diet-induced metabolic associated fatty liver in mice through modulation of gut microbiota and host metabolism.

BACKGROUND AND AIM: Gut-liver axis dysfunction drives metabolic associated fatty liver disease (MAFLD), but effective therapeutic strategies remain limited. Bletilla striata oligosaccharides (BSO) have immunomodulatory potential, yet their role in MAFLD via the gut-liver axis is unclear. This study aimed to investigate whether and how BSO ameliorates MAFLD by modulating gut microbiota, intestinal barrier function, and hepatic inflammation.

RESULTS

MAFLD was induced in mice by 8-week high-fat diet followed by 12-week BSO (150, 300, 600 mg/kg) or metformin treatment via oral gavage. Compared with the MAFLD model, high-dose BSO reduced body weight gain, lowered fasting glucose, and decreased hepatic triglycerides. BSO also attenuated liver injury, hepatic steatosis, inflammation. Mechanistically, BSO restored gut barrier integrity, upregulated colonic tight junction proteins, activated colonic LXRα/ABCA1 signaling, while suppressing the hepatic TLR4/NF-κB pathway. BSO remodeled gut microbiota, enriching beneficial Lachnospiraceae and Oscillospiraceae, and modulated hepatic metabolites, as shown by decreased confertifoline along with increased D-myo-inositol-4-phosphate. Additionally, BSO activated the intestinal FXR/FGF15 axis and ameliorated bile acid metabolism disorders, evidenced by reduced tauro-ω-muricholic acid and cholic acid.

CONCLUSION

This study provides systematic evidence that BSO alleviates MAFLD through a multi-target gut-liver axis mechanism involving gut microbiota remodeling, barrier restoration, activation of LXRα/ABCA1 and FXR/FGF15 signaling, and subsequent suppression of hepatic TLR4/NF-κB-driven inflammation. Compared to previous approaches, BSO offers a favorable safety profile with combined regulatory effects. These findings support BSO as a promising candidate for MAFLD treatment, with potential applications as a dietary supplement or prebiotic agent.