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In contrast, <jats:italic>Prevotella<\/jats:italic> and <jats:italic>Megamonas<\/jats:italic> were substantially decreased, and <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Phocaeicola<\/jats:italic> were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings provide new insights into the intricate interplay between the gut and microbiome\u2010brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. 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