Intergenerational association of gut microbiota and metabolism with perinatal folate metabolism and neural tube defects

Disorders of folic acid metabolism during pregnancy lead to fetal neural tube defects (NTDs). However, the mechanisms still require further investigation. Here, we aim to analyze the brain metabolic profiles of 30 NTDs and 30 healthy fetuses. Our results indicated that low-folate diet during early life played a causal role in cerebral metabolism, especially in lipometabolic disturbance, highlighting the importance of folate in modulating brain development and metabolism. Next, we established a mouse model of NTDs. Interestingly, the differential metabolites are mainly involved in glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids both in human and mice fetal brain. Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, we further found the abundances of Firmicutes and Bacteroidetes in the gut of pregnant mice were correlated with the abundances of lipid metabolism related metabolites in the fetal brain. This finding probably reflects the intergenerational microbial-metabolism biomarkers of NTDs.