Prenatal Maternal Stress and Infant Gut Microbiome in Human and Animal Studies: A Comprehensive Systematic Review.

The infant gut microbiome plays a fundamental role in immune maturation, metabolic programming, and neurodevelopment, with early microbial colonization representing a sensitive period for long-term health outcomes. Maternal factors during pregnancy powerfully modulate infant microbiome assembly; however, the specific effects of prenatal stress exposure (PSE) on offspring gut microbial communities remain incompletely understood. Here, we present a cross-species systematic review, the first of this scale, examining associations between prenatal stress and offspring gut microbiome composition. Searches of PubMed (MEDLINE), Scopus, and PsycINFO identified 33 review-eligible articles published over the past two decades. Across studies, we evaluated stressor characteristics, offspring age at microbiome assessment, and methodological issues relevant to result interpretation. Although the literature is heterogeneous and reports mixed findings, several recurring patterns emerge. Most studies report an increased relative abundance of Proteobacteria and reduced levels of early-life beneficial taxa from the Actinobacteria and Firmicutes phyla following PSE, driving a negative shift toward a pro-inflammatory profile and early-life dysbiosis. At the genus level, decreases in Bifidobacterium, Lactobacillus, Muribaculum, and Parabacteroides are frequently observed, alongside increases in Klebsiella, Enterobacter, and Sutterella, taxonomic shifts that disrupt gut homeostasis and are associated with increased lifelong risks for metabolic, inflammatory, and neurodevelopmental disorders. Differences between human cohorts and animal models regarding alpha diversity patterns and beta diversity clustering are identified. Finally, we explore methodological limitations in the existing literature and discuss recent advances and recommendations to support the continued development of research on prenatal stress, the gut microbiome, and developmental outcomes. Altogether, our study demonstrates that while PSE acts as a powerful upstream ecological modifier of the early-life gut microbiota across species, its long-term biological embedding is heavily moderated by sex, developmental timing, and specific environmental context.