The Role of the Microbiota-Gut-Brain Axis in Perinatal Depression: Novel Insights for Treatment

Abstract: Perinatal depression, a prevalent mood disorder complicating pregnancy and childbirth, poses significant threats to maternal health and neonatal development. While psychotherapy and antidepressants constitute current standard treatments, their clinical application faces substantial limitations during pregnancy and lactation, including safety concerns, treatment resistance, and poor adherence rates. These therapeutic constraints have spurred growing interest in novel gut-brain axis (GBA)-targeted interventions. Emerging evidence suggests that the gut microbiota communicates with the brain through a complex network of neural, immune, and endocrine pathways, playing a critical role in regulating mood, behavior, and cognitive functions. Interventions such as probiotics and fecal microbiota transplantation (FMT) are increasingly explored for their potential to restore microbial balance and alleviate depressive symptoms. This review aims to systematically examine the role of the GBA in the context of perinatal depression, offering novel insights to inform clinical treatment strategies. Furthermore, it evaluates the promise and limitations of microbiota-targeted interventions while discussing future directions for personalized microbiome therapeutics.