Intergenerational effects of the microbiota on neurodevelopment: mechanisms and therapeutic perspectives
Abstract
Neurodevelopment is governed by precisely timed biological processes that are sensitive to environmental influences across generations. Among these, the gut microbiota (GM) has emerged as a key regulator of neurodevelopmental trajectories, not only within individuals but also through intergenerational transmission. This review highlights the emerging significance of the GM in shaping offspring brain and behavior, emphasizing its capacity to mediate maternal influences across generations. We first summarize the temporal and intergenerational effects of GM on host physiology and neurobehavioral outcomes. We then explore the mechanistic basis of neuro-microbial-immunometabolic interactions including epigenetic regulation, neurotransmitter modulation, neuroinflammation and intestinal barrier function in the context of the microbiota-gut-brain axis. Particular attention is given to how these mechanisms mediate the long-term impact of maternal states—such as stress, diet and inflammation—on offspring neurodevelopment. We further highlight the translational gap from animal models to humans and propose integrating multi-omics, computational modeling, and clinical approaches to define developmental windows and guide precision microbiota-based interventions for neurodevelopmental disorders. By elucidating how microbiota influence neurodevelopment across generations, this review aims to inform the development of novel microbial and pharmacological therapies to promote brain health from the maternal period through early offspring life.
Keywords:
neurodevelopment; intergenerational; gut microbiota; gut-brain axis; microbiota-based intervention; neuro- immunometabolism