Lactiplantibacillus plantarum Q180 Mitigates Early High-Fat Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Gut–Liver Axis Inflammation and Barrier Integrity

Metabolic dysfunction-associated steatotic liver disease (MASLD) develops through systemic metabolic dysregulation and gut–liver axis-mediated inflammation; however, effective preventive strategies remain limited. Probiotics such as Lactiplantibacillus plantarum have emerged as potential modulators of intestinal barrier integrity and hepatic inflammation; however, preventive efficacy during early MASLD progression has not been fully elucidated. The present study evaluated whether L. plantarum Q180 attenuates early high-fat diet (HFD)-induced MASLD in a murine model. Male C57BL/6J mice were fed a normal diet or 60% HFD for 12 weeks, and Q180 was orally administered at 1.0 × 10 9 CFU/day from weeks 5 to 12. HFD feeding induced obesity, hepatic lipid accumulation, and an elevated nonalcoholic fatty liver disease activity score (NAS), confirming early-stage MASLD. Although Q180 did not significantly reduce body weight gain or adipose tissue mass, Q180 did significantly decrease hepatic triglyceride levels and NAS, accompanied by improvements in steatosis, hepatocellular ballooning, and inflammatory infiltration. Hepatic expressions of Dgat1 and Sod were significantly upregulated, whereas Ldlr expression was downregulated. In the colon, Q180 markedly suppressed Tnf-α and Il-6 expression and partially restored Zo-1 , Occludin , and Muc2 expressions. Serum endotoxin levels were significantly reduced, and a decreasing trend was observed in fecal endotoxin levels. Overall, Q180 exerted metabolic and immunological benefits during early MASLD progression by reducing hepatic lipid accumulation, enhancing antioxidant defenses, attenuating intestinal inflammation, reinforcing intestinal barrier integrity, and lowering endotoxin exposure. The results support Q180 as a promising probiotic candidate for the prevention and early management of MASLD through gut–liver axis modulation.