Influences of ampicillin exposure in early life on the murine gut microbiota and steatotic liver disease associated with western diet.

Dysbiosis of gut microbiota is one of the important factors associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Antibiotic use, especially in early life, could profoundly disrupt an establishing process of stable gut microbiota, and the influence on gut environment may persist throughout life. In this study, we examined effects of ampicillin exposure (AMP) in early life on the temporal changes of fecal microbiota and severity of MASLD in western diet-fed C57BL/6J mice. Histological evaluation of MASLD showed that steatosis in female mice and lobular inflammation was significantly influenced with AMP, and that NAS (MASLD activity score constituting from score of steatosis, lobular inflammation, and ballooning degeneration) tended to be high in female of AMP-treated group. 16S metagenome analyses of fecal microbiota showed significant decrease of α-diversity and remarkable shift to normally minor bacterial species at 4 weeks of age in AMP-treated mice, and the influence was continuously observed even after finishing the western diet feeding period. α-Diversity at 4weeks of age negatively correlated with combined scores of steatohepatitis and fibrosis. These results suggest that AMP in early life induced dysbiosis of gut microbiota and could promote the development of western diet-associated steatotic liver disease. J. Med. Invest. 73 : 186-207, February, 2026.