Active Hexose Correlated Compound Modulates Gut Microbiota and Improves Intestinal Barrier Function in a High‐Fat Diet‐Induced NAFLD in Rats

Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide, correlating with increased obesity and metabolic disorders. Gut microbiota dysbiosis and impaired intestinal barrier integrity are key factors in NAFLD pathogenesis. Active hexose correlated compound (AHCC), a standardized extract from cultured Lentinula edodes mycelia, has shown immunomodulatory effects, but its impact on gut microbiota and intestinal function in NAFLD remains unclear. This study evaluated AHCC supplementation's effects on gut microbiota composition and intestinal barrier integrity in a high-fat (HF) diet-induced NAFLD rat model. Thirty-two male Sprague-Dawley rats were divided into control diet (CD), HF diet, and HF diet + 2% AHCC groups for 6 weeks. AHCC supplementation significantly altered gut microbiota, increasing alpha diversity and shifting clustering patterns. It increased Blautia hansenii and Blautia producta abundance, known for antiinflammatory and antiobesity properties. These changes correlated with improved intestinal barrier integrity, evidenced by upregulation of Mucin 2 (MUC2) and a trend toward increased tight junction protein expression. AHCC reduced local inflammation in the colon and liver and attenuated systemic inflammation. These findings suggest that AHCC supplementation can modulate gut microbiota composition, thereby mitigating oxidative stress, regulating inflammation, and improving intestinal barrier integrity in HF diet-induced NAFLD.