{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329693/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329693"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Microbiome-Derived Metabolites Shape CD4⁺ T-Cell Differentiation and Immune Aging in Chronic HIV-1 Infection [RNA-Seq]","description":"The role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4⁺ T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4⁺ T-cell metabolic and functional states. Among these metabolites, p- cresol sulfate (PCS) emerged as a mechanistic prototype investigated in depth. Ex vivo flow cytometry and single-cell RNA sequencing of CD4⁺ T-cells stratified by cell-associated PCS levels revealed dose-dependent enrichment of transcriptional programs associated with impaired differentiation capacity, regulatory-like identity, and cellular senescence. Consistently, in vitro transcriptomic and proteomic analyses of PCS-exposed CD4⁺ T cells demonstrated induction of cell-cycle arrest, mitochondrial dysfunction, and senescence-associated programs, including upregulation of p16 and p21. Integration of these immunometabolic features with measurements of HIV-1 reservoir size in PLWH revealed that CD4⁺ T-cell states defined by cell-associated GDBMs track with intact proviral DNA levels in vivo. Together, these findings define a microbiome-derived axis that reshapes CD4⁺ T-cell metabolism and fate and promotes immune aging–associated states in PLWH. Our data suggest that cell-associated GDBMs may foster immunometabolic CD4⁺ T-cell states previously linked to long-term HIV-1 reservoir persistence in vivo.","dates":{"publication":"2026/06/15"},"accession":"GSE329693","cross_references":{"GSM":["GSM9709360","GSM9709382","GSM9709381","GSM9709362","GSM9709361","GSM9709380","GSM9709368","GSM9709367","GSM9709348","GSM9709369","GSM9709347","GSM9709364","GSM9709363","GSM9709366","GSM9709365","GSM9709349","GSM9709371","GSM9709370","GSM9709351","GSM9709373","GSM9709372","GSM9709350","GSM9709357","GSM9709379","GSM9709378","GSM9709356","GSM9709359","GSM9709358","GSM9709375","GSM9709353","GSM9709374","GSM9709352","GSM9709377","GSM9709355","GSM9709354","GSM9709376"],"GPL":["24676"],"GSE":["329693"],"taxon":["Homo sapiens"]}}