Prenatal Intake of High Multivitamins or Folic Acid With or Without Choline Contributes to Gut Microbiota-Associated Dysregulation of Serotonin in Offspring

Abstract

The gut microbiota is amenable to early nutrition including micronutrients but intake above and below the recommendations commonly occur with unknown consequences. Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine found centrally and peripherally with diverse functions such as food intake regulation via the hypothalamic 5-HT receptor 2C (5-HTR2C). This study determined the impact of prenatal micronutrients on the gut microbiota and serotonergic system in offspring. Pregnant Wistar rats were fed either recommended vitamins (RV), high vitamins (HV), high folic acid with recommended choline (HFRC), or high folic acid with no choline (HFNC). Offspring were fed a high-fat diet for 12 weeks postweaning. HV, HFRC, and HFNC males and females had lower hypothalamic 5-HTR2C protein expression compared to RV. Brain 5-HT concentrations were lower but colon 5-HT concentrations were higher in HV and HFNC males and females and HFRC males compared to RV. Refeeding response after 5-HTR2C agonist was negatively correlated with hypothalamic 5-HTR2C protein expression in males and with brain 5-HT concentrations in females. Random forest revealed top bacterial taxa, which Lactococcus, Ruminococcus, Bacteroides, and Oscillospira showed significant correlations with refeeding response and concentrations of brain and colon 5-HT. In conclusion, excess or imbalanced prenatal consumption of micronutrients leads to gut microbiota-associated disturbances in the serotonergic system in offspring.