Shaozhi Liu, Senling Feng, Zhongwen Yuan, Zhengrong Mei, Jinjin Yin, Lei Chen, Yongxia Zhang
Maternal nutrition during pregnancy is a critical determinant of offspring long-term health. Dietary fiber has emerged as a key modifiable factor. Through gut microbial fermentation, fiber is converted into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate. This mini review synthesizes current evidence from molecular, animal, and human studies on the role of maternal SCFAs in programming offspring metabolic and immune health. Mechanistically, SCFAs act via two complementary pathways: activation of G protein-coupled receptors (GPCRs) and inhibition of histone deacetylases, leading to rapid signaling and long-term epigenetic regulation. Animal studies demonstrate that maternal fiber deprivation impairs offspring glucose metabolism, promotes low-grade inflammation and obesity, and compromises immune tolerance, whereas fiber or short-chain fatty acid (SCFA) supplementation confers protective effects. Human observational studies support these findings, showing associations between maternal SCFA levels and favorable neonatal metabolic profiles, neurodevelopmental outcomes, and reduced obesity risk, although randomized controlled trials remain limited. Key translational challenges include inter-species differences, individual microbiome variability, and optimal intervention timing. Despite these uncertainties, promoting adequate and diverse dietary fiber intake during pregnancy represents a safe, low-cost, and scalable public health strategy to improve intergenerational health outcomes.