Gut Microbiome Changes In Mice Exposed to Benzo[a]Pyrene During Early Brain Development Dependent on Cyp1a1 Genotype

Benzo[a]pyrene (BaP) is a carcinogenic polycyclic aromatic hydrocarbon commonly found in traffic-related air pollution, tobacco smoke, and grilled foods. BaP is linked to learning deficits and to neurodevelopmental delays in human and animal studies. Studies have also shown that changes in the gut microbiome health can affect cognition. We are using a mouse model to determine if genetic differences increase susceptibility to BaP exposure during early brain development. Cyp1a1(-/-) knockout mice and wild type Cyp1a1(+/+) mice were exposed to 10mg/kg/day BaP from gestational day 10 (GD10) through weaning at postnatal day 25 (P25). Feces from the dam, two male pups (pooled), and two female pups (pooled) were collected overnight at postnatal day 24 using metabolic cages. DNA extraction was performed by NKU undergraduates, and 16S rRNA bacterial amplicons were sequenced and analyzed at the University of Louisville Genomics without follow-up analysis by NKU undergraduates. BaP-exposed Cyp1a1(-/-) knockout mice were significantly different from all other groups. There were no significant differences between control and BaP-exposed wild type Cyp1a1(+/+) mice. Functional annotation was performed using PICRUSt2 software. Interestingly, three of the top 20 differences in the pathway analysis involved degradation of the amino acid tryptophan. This suggests possible disruption of normal pathways used to produce the neurotransmitter serotonin, which is derived from tryptophan and provides a potential mechanism to explain our previously reported changes in serotonin levels in the brains of BaP-exposed mice