APOE genotype and chlorpyrifos: Examination of their roles in gut dysbiosis and influence on metabolites in the brain Charlene Hoang
During birth to adulthood the gut microbiome can undergo a series of changes (Backhed et al., 2015), and dysbiosis of the gut microbiota is a result of diet changes, lifestyle changes, genetic factors and environmental factors and is a target of study for neurodevelopmental disorders like Alzheimer’s Disease. Guardia-Escote et al. (2020) explores the Apolipoprotein E (APOE) gene’s isoforms apoE3 and apoE4 – apoE4 is a genetic risk factor for Alzheimer’s Disease (Hersi et al., 2017) – and their suspected roles in modulating gut microbiota composition. They further explored dysbiosis and metabolite level changes in response to exposure to chlorpyrifos (CPF), a commonly used pesticide found at low levels in our diet, which was administered postnatally between days 10-15. Short-chain fatty acid (SCFA) levels and genomic differences of gut microbiota were examined across three transgenic mouse types – C57BL/6, apoE3-TR, and apoE4-TR at postnatal day 15. ApoE4-TR mice were found to have significantly reduced levels of A. muciniphilla, luteolibacter, and rubritaleo in response to CPF exposure and apoE3-TR mice were found to have increased levels of SCFAs including isovaleric acid and 4-methylvaleric acid. The results suggest that the gut microbiota can be altered substantially at early stages of development by both common genetic and environmental factors, and that alterations of metabolites like SCFA in the brain can lead to neurodevelopmental disorders later in life. Keywords: Apolipoprotein E (APOE), chlorpyrifos (CPF), dysbiosis, short-chain fatty acid (SCFA), gut microbiota, Alzheimer’s Disease
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