Athlete-derived fecal microbiota transplantation ameliorates high-fat diet-induced fatty liver and mitochondrial dysfunction in mice

초록

Background: High-fat diet (HFD) is a major contributor to the development of nonalcoholic fatty liver disease (NAFLD), leading to hepatic steatosis, insulin resistance, and mitochondrial dysfunction. Emerging evidence highlights the regulatory role of gut microbiota in host metabolism. This study aims to assess the metabolic effects of fecal microbiota transplantation (FMT) derived from female track and field athletes on hepatic glucose metabolism, lipid accumulation, and mitochondrial function in a mouse model of HFD-induced NAFLD. Methods: C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce fatty liver. From weeks 5 to 12, fecal microbiota from female track and field athletes was orally administered weekly to FMT groups. Exercise groups performed treadmill running (20 m/min, 60 min/day, 5 days/week). Experimental groups included: control (CON), antibiotics (ABS), HFD, HFD with FMT (fHFD), HFD with FMT and exercise (fHFX), and HFD with exercise (HFX). Glucose metabolism, insulin signaling (AKT/pAKT), hepatic inflammation, mitochondrial function, liver histology, and intestinal morphology were analyzed Results: FMT alone (fHFD group) significantly improved glucose tolerance and AKT phosphorylation and reduced hepatic TNF-a and IL-6 expression (p < .05), showing comparable effects to those observed in the exercise-only group (HFX). Both interventions led to reduced hepatic lipid accumulation and improved mitochondrial respiration. Notably, the combined FMT and exercise group (fHFX) exhibited the greatest improvements across all parameters, including liver histology and intestinal morphology, indicating a synergistic effect (p < .05). Conclusion: Fecal microbiota transplantation from female athletes exerted beneficial metabolic effects similar to those of treadmill exercise in HFD-induced fatty liver. When combined, FMT and exercise produced synergistic improvements in glucose metabolism, hepatic inflammation, lipid accumulation