Maternal microbiota and fetal brain development: a multidisciplinary review of cognitive, neurological, and metabolic outcomes

Abstract

The prenatal period represents a critical window for the programming of the central nervous system. This multidisciplinary narrative review aims to synthesize current evidence regarding the maternal microbiota-gut-fetal brain axis, examining how maternal gut composition may influence fetal neurogenesis, synaptogenesis, and long-term neurobehavioural outcomes. We analyse three primary pathways of influence: the systemic translocation of neuroactive bacterial metabolites (specifically short-chain fatty acids), the modulation of the maternal immune system leading to maternal immune activation (MIA), and the endocrine regulation of the hypothalamic–pituitary–adrenal axis. These pathways are interconnected and their synergistic effects are considered throughout. Neurological data, predominantly from animal models, suggest that maternal dysbiosis may disrupt microglial maturation and cortical lamination through epigenetic modifications mediated by butyrate and serotonin precursors. Endocrinological evidence highlights the role of the estrobolome and the bacterial conversion of glucocorticoids into neuroactive progestins. Obstetric and pediatric findings indicate associations between maternal microbiome composition, preterm birth risks, and the incidence of autism spectrum disorders and ADHD in offspring, though causal inference from human data remains limited. Nutritional analysis suggests that dietary fibers and Omega-3 fatty acids may act as modulators of this axis. The maternal microbiota is a potentially modifiable determinant of fetal neurological health. Microbiome-based interventions carry potential risks and require careful clinical evaluation. A comprehensive, individualized approach integrating neurology, endocrinology, obstetrics, and nutrition is required to develop evidence-based preventive strategies.