<b>Bidirectional </b><b>AHR-</b><b><i>A. muciniphila </i></b><b>axis </b><b>mediates </b><b>the alleviation of alcohol-induced cognitive and social dysfunction</b>

Alcohol-induced cognitive and social dysfunction (AICSD) constitutes a primary etiology of early-onset dementia but with limited effective therapeutic approaches. Recently, the metabolic interactions between host and gut microbiota have emerged as mechanistic pathways implicated in the development of alcohol-related diseases. Here, we report that activation of the aryl hydrocarbon receptor (AHR) alleviated alcohol-related cognitive and social dysfunction. Moreover, activation of AHR significantly enhanced the abundance of <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>), which was positively correlated with the host behavioral alterations. Furthermore, treatment with A. muciniphila also effectively ameliorated AICSD. Finally, our findings demonstrate a communication bidirectionally between <i>A. muciniphila</i> and AHR in mediating alcohol-induced cognitive and social impairments. Collectively, our results reveal a bidirectional AHR-<i>A. muciniphila</i> axis for alleviating AICSD, providing valuable insights for developing AHR and microbiome-targeted therapeutic strategies against alcohol-induced neurodegenerative diseases.