Abstract WMP109: Aged Maternal Biome Impairs Offspring Health

Abstract

Background: The gut and its microbiome have become highlighted because of their holistic effect on the body in health and disease. The bi-directional communication of the gut-brain axis is highly involved in, among others, the immune response. Additionally, the maternal gut microbiome affects offspring brain, immune system, and gut microbiome formation and development. Therefore, an aged and unhealthy maternal biome that is may increase both stroke risk factors among offspring. Method: Young female C57B6 mice 3-month (M) of age had their host gut bacteria cleared via antibiotic treatment prior to recolonization via fecal microbiome transplants from 3M control, and 18M reproductively senescent female mice. The subsequent offspring was aged to 18 months, followed by behavioral tests, glucose tolerance, and blood pressure measurement, prior to a transient 90-minute middle cerebral artery occlusion (MCAO). Results: Compared to control females with 3M biome, females with an aged biome had decreased fecundity from 26.4 days to 54.75 days at the onset of breeding to birth of pups (p=0.0018). There was no change in estrus cycle between the groups. The offspring gut microbiome had been affected in a sex specific manner. Female pups from dysbiotic, aged, biome mothers differed significantly in terms of b-diversity compared to those from control mothers (p=0.009) with pathogenic increases to firmicutes shifting the F:B ratio. There was a less pronounced trend in male offspring (p=0.241). Interestingly, no weight differences were observed in offspring depending on the maternal biome. At 2M of age, a depressive phenotype in tail suspension test was noted for male(p=0.0001) and female (p=0.0059). However, at 6M and older, the depressive phenotype subsided. Male offspring at 18M demonstrated a significant change (p=0.0001) in Glucose tolerance test compared to age matched females. Conclusion: The maternal microbiome has a significant impact on offspring biome composition and health. Mice from mothers with aged microbiome exhibited early life depressive phenotypes, slower glucose metabolism, and a pathogenic gut microbiome composition. Therefore, maternal gut has transgenerational health effects which may be exacerbating stroke risk and potentially outcome.