Abstract

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Conception, gestation, and lactation are critical periods for human development. The exposure to unhealthy dietary patterns, excess weight gain and other environmental factors results in a higher risk of pregnancy complications affecting both mothers and infants. We propose that the microbiota mediates many risks and that in some circumstances, its manipulation might have a protective effect. The exact mechanisms remain unknown, but we know that specific host physiology and behaviors result in distinct microbiomes during pregnancy, thereby influencing maternal–neonatal health and programing infant development. The direct microbiota–host interactions and microbiota functionality warrant further research, especially in different environmental (diet) and disease (gestational diabetes mellitus, GDM) contexts.

The specific objectives of the project are: (1) to deeply characterize the maternal microbial (vaginal, oral, fecal) and functional (metabolomics) profiles during pregnancy for two geographically diverse cohorts in Mediterranean area (Spain, Israel) and relate them with maternal diet composition, maternal-neonatal clinical data and neonatal health outcomes (gestational age at birth, birthweight); (2) to identify the impact of external factors, specifically diet, on the maternal microbiomes during pregnancy, with a focus on GDM; and (3) to determine the gut microbiota’s role in mediating diet control of GDM using a germ-free murine model and fecal microbiota transplant experiments.

A systems biology approach featuring state-of-the-art sequencing techniques, metabolomics, and modeling will be employed to map microbiota dynamics in pregnancy across cohorts and in light of GDM status and dietary intervention. Human observational and longitudinal cohorts from the two geographically distinct regions will be used to identify specific "markers" associated with the microbe-diet interplay during pregnancy, and work with animal models will provide causational evidence for uncovered patterns.

This multidisciplinary approach will identify nutritional guidance and key biomarkers that support positive interactions between microbes, perinatal factors, and the host response during pregnancy. It will serve to highlight evidence-based directions for future health programming, like GDM interventions, that enable new applications in relation to personalized nutrition and medicine intended to enhance women’s and children’s health. Therefore, our research is intended to identify sustainable, holistic life-style solutions to reduce pregnancy complications, as a public health priority focused on maternal-neonatal microbiota and health.

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