show Abstracthide AbstractHIV-associated neurocognitive disorder (HAND) is a complex neurodegenerative disease whose underlying mechanism remains unclear. Recent studies have highlighted the critical role of the gut microbiota in contributing to neurodegenerative disorders through the gut-microbiome-brain axis. To investigate the potential involvement of the gut microbiota in the pathogenesis of HAND, we conducted metagenomic sequencing of 84 fecal samples (HAND, n=30; HIV-non-HAND, n=27; and HC, n=27) to examine the composition of the gut microbiome. Additionally, we performed metabolomics based on liquid chromatography-mass spectrometry (LC/MS) of plasma samples to assess alterations in metabolites in HAND.