Early-life gut microbiota and neurodevelopment in preterm infants: any role for Bifidobacterium?

Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut–brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.

Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies. • Microbiota, immune, and neurophysiological profile of 60 extremely premature infants • Pro-inflammatory T cell response correlates with suppressed electrocortical maturation • γδ T cells have central implications for the pathogenesis of brain injury • Klebsiella overgrowth in the gastrointestinal tract is predictive for brain damage Seki et al. performed a comprehensive, time-resolved analysis of the gut microbiota-immune-brain axis in extremely premature infants. This analysis links early-life microbiome establishment to immunological and neurological development, identifying candidate biomarkers of perinatal brain injury and promising targets for personalized treatments to alleviate, or even prevent, life-long neurological morbidities.

Key Points Question What are the long-term outcomes associated with dysbiosis of gut microbiota in very preterm newborns? Findings In this cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort, gut microbiota at week 4 after birth showed 6 bacterial patterns that varied according to gestational age, perinatal characteristics, individual treatments, and neonatal intensive care unit strategies. Three clusters were associated with 2-year outcomes after adjustment for these confounders. Meaning Modifying strategies associated with alterations in microbiota, such as promoting enteral nutrition, reducing sedation use, promoting early extubation, or skin-to-skin practice, may be correlated with outcomes in preterm newborns.