Maternal obesity induces sex-specific gut microbiota changes associated with reduced fecal levels of endocannabinoid-like molecules in rat offspring at weaning

Abstract

Maternal obesity alters the gut microbiota of offspring, although sex-specific effects remain poorly assessed before puberty. An interplay has emerged between the gut microbiota and fecal endocannabinoids, including oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which exert anti-inflammatory and anti-obesity effects. We have demonstrated that maternal obesogenic diet induces early obesity associated with low fecal PEA and OEA levels and sex-specific changes on the gut endocannabinoid signaling of offspring at weaning. We hypothesized that maternal obesity induces sex-specific gut microbiota. Progenitor female rats were divided maternal control group (received control diet) or maternal obesity group (received obesogenic diet, high-fat high-sugar diet) during perinatal period. Gut microbiota analysis was performed using feces from offspring at weaning. There was no sexual dimorphism in the gut microbiota between control female offspring and control male offspring. Maternal obesity increased the Blautia abundance and decreased Mucispirillum abundance in the gut microbiota in males compared to control male offspring. Blautia abundance showed a negative correlation, while Mucispirillum abundance showed a positive correlation with PEA and OEA fecal levels. There were no correlations between gut microbiota and offspring adiposity, which was negatively correlated with PEA and OEA fecal levels. In conclusion, only in male offspring, maternal obesity-induced gut microbiota changes, which could contribute to low PEA and OEA fecal levels and early obesity. Fecal endocannabinoids could reflect the biological mechanism by which gut microbiota impacts adiposity in early life. Our findings provide molecular insights into the sex-specific crosstalk between gut microbiota and fecal endocannabinoids underlying intergenerational metabolic disorders.