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 <i>Agathobacter</i>, which were negatively correlated with cognitive impairment. Animal experiments showed that <i>Agathobacter rectalis (A. rectalis)</i> 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 <i>A. rectalis</i>, reduced microglial activation and pro-inflammatory factor production via Akt/ nuclear factor κB (NF-κB) signal pathway <i>in vitro</i>. Meanwhile, we revealed that <i>A. rectalis</i> effectively inhibited activation of microglia in the APP/PS1 mice by regulating Akt/ NF-κB pathway. This finding highlights the role of <i>A. rectalis</i> and its metabolite butyrate in mitigating neuroinflammation in AD by modulating the Akt/NF-κB pathway.