Early life is fundamental for brain and microbiota development. Gut microbiota influences brain function. Maternal obesity affects maturation of gut microbiota and is an important predictor of cognitive dysfunction in the offspring. Cognitive decline through life is an increasingly invalidating condition, due to population ageing and the high frequency of predisposing factors (obesity, unhealthy diets). We hypothesized that the negative effects of maternal obesity on cognitive function in the offspring are partly mediated by the microbiota and its metabolites, offering the opportunity for non-invasive risk-screening and -reduction by tailored foods and diets, since earliest life stages. We used two existing cohorts of children to provide leads, and preclinical models to prove cause-effect relationships, and develop tailored dietary interventions to counteract the effects of maternal obesity on cognition. GUTMOM involved academic centres, and a private industrial collaborator providing project co-funding. Our results indicate that maternal high-fat diet (HFD) and early-life stress (ELS) were more impactful than maternal body weight on offspring's health in mice; we identified bacteria and fecal metabolites that predicted cognition in children, and showed that fecal transplantation into mice reproduced a correlated phenotype. We also showed that ELS has an important impact on fecal microbiota and metabolites, with gender differences, and that antioxidant treatment during pregnancy is more beneficial for brain BDNF and CD68 expression in female than male mice born to HFD dams. The plan included intensive dissemination and training activities for young scientists, and the study has contributed to the ongoing Knowledge Platform on Diet, Intestinal Microbiomics and Health.

Results indicate: 1) a positive effect of breastfeeding (in girls) or prescholar adherence to a mediterranean diet on selected neurodevelopment domains; 2) maternal BMI effects on microbiota and neurodevelpment in early childhood, but mice and human studies suggest that HFD during pregnancy is more impactful in adulthood than maternal BMI, and 3) a predictive value of meconium bacteria on prescholar neurodevelopment, and 4) of selected fecal metabolites (also related with exclusive breast-feeding), as measured contextual to cognitive function at precholar age; 5) the transfer of prescholar children-donors' phenotype into recipient germ-free mice, via microbiota transplantation; 6) an impact of maternal HFD, ELS and the combination on offspring's body weight, especially in males, and 7) a strong impact of ELS on microbiota, especially in females, and fecal metabolome, especially in males, as well as on the microbiota-metabolome association; 8) efficacy of prenatal (maternal) administration of the antioxidant N-acetyl-cysteine (NAC) to prevent the negative effects of maternal HFD, by buffering adverse changes in brain BDNF and CD68 expression in female mice.