Intergenerational association of gut microbiota and metabolism with perinatal folate metabolism and neural tube defects
Shan Wang,
Xuejia He,
Yi Wang,
Yubing Zeng,
Pei Pei,
Xiaojun Zhan,
Min Zhang,
Ting Zhang
Affiliations
Shan Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing 100020, China; Corresponding author
Xuejia He
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing 100020, China
Yi Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Yubing Zeng
Children’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China
Pei Pei
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Xiaojun Zhan
Otorhinolaryngologic Department, Capital Institute of Pediatrics, Beijing 100020, China
Min Zhang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Corresponding author
Ting Zhang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing 100020, China; Corresponding author
Summary: 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.
