The maternal diet during pregnancy is an important factor that influences the intrauterine environment during fetal development. However, the relationship among maternal diet, the gut microbiome of offspring, and health outcomes remains unclear. Here, we report that changes in the gut microbiome of offspring after maternal exposure to 50% food restriction and 45% high-fat diet during pregnancy can affect the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring in a sex-specific manner. Notably, despite no significant difference in body weight, plasma triglyceride and leptin levels were significantly increased in male offspring compared with the controls. The relative abundance of the butyrate-producing genera of the Lachnospiraceae family was dependent on the sex of the offspring and correlated with plasma triglyceride and leptin levels. Interestingly, male offspring in the 50% restricted diet or 45% high-fat diet groups had reduced butyrate levels compared with the control group and were affected by oxidative damage and hepatic lipogenesis. Our findings suggest that the maternal diet during pregnancy affects the gut microbiota of male offspring in a sex-specific manner, potentially predisposing them to MASLD later in life through dysregulation of lipid metabolism.
Keywords: fetal programming; gut microbiome; lipid metabolism; metabolic diseases; short‐chain fatty acids.
© 2025 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.