The gut microbiota modulates environmental risk for cognitive impairment
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ABSTRACT:
PROVIDER: PRJNA684902 | ENA |
REPOSITORIES: ENA
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Project description:Cognitive impairment (CI) is a prevalent neurological condition characterized deficient attention, causal reasoning, learning and/or memory. Many genetic and environmental factors increase risk for CI, and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms of action remain unclear. Here we examine the gut microbiome in response to restricted diet and intermittent hypoxia, known environmental risk factors for CI. Modeling the environmental factors together in mice potentiates CI and alters the gut microbiota. Depleting the microbiome by antibiotic treatment or germ-free rearing prevents the adverse effects of environmental risk on CI, whereas transplantation of the risk-associated microbiome into naïve mice confers CI. Parallel sequencing and gnotobiotic approaches identify the pathobiont Bilophila wadsworthia as enriched by the environmental risk factors for CI and as sufficient to induce CI. Consistent with CI-related behavioral abnormalities, B. wadsworthia and the risk-associated microbiome disrupt hippocampal activity, neurogenesis and gene expression. The CI induced by B. wadsworthia and by environmental risk factors is associated with microbiome-dependent increases in intestinal IFNy-producing Th1 cells. Inhibiting Th1 cells abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction.
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