Gut commensal Agathobacter rectalis alleviates microglia-mediated neuroinflammation against pathogenesis of Alzheimer disease

Gut microbiota plays a crucial role in the pathogenesis of Alzheimer disease (AD). Here, we found that AD patients had significantly lower abundance of Agathobacter, which were negatively correlated with cognitive impairment. Animal experiments showed that Agathobacter rectalis (A. rectalis) supplementation increased beneficial commensal bacteria, significantly improved pathological damage, and suppressed microglial activation in APP/PS1 mice. We further demonstrated that butyric acid, a metabolite of A. rectalis, reduced microglial activation and pro-inflammatory factor production via Akt/ nuclear factor κB (NF-κB) signal pathway in vitro. Meanwhile, we revealed that A. rectalis effectively inhibited activation of microglia in the APP/PS1 mice by regulating Akt/ NF-κB pathway. This finding highlights the role of A. rectalis and its metabolite butyrate in mitigating neuroinflammation in AD by modulating the Akt/NF-κB pathway.