Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1
Abstract Background Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood. Methods In this c...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12967-025-06168-0 |
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| author | Lin-Yu Wan Sin Man Lam Hui-Huang Huang Wen-Jing Cao Xiang-Yi Cao Xue-Meng Li Li-Ping Zhang Jia-Min Gao Chao Zhang Xing Fan Yan-Mei Jiao Guanghou Shui Fu-Sheng Wang Jin-Wen Song |
| author_facet | Lin-Yu Wan Sin Man Lam Hui-Huang Huang Wen-Jing Cao Xiang-Yi Cao Xue-Meng Li Li-Ping Zhang Jia-Min Gao Chao Zhang Xing Fan Yan-Mei Jiao Guanghou Shui Fu-Sheng Wang Jin-Wen Song |
| author_sort | Lin-Yu Wan |
| collection | DOAJ |
| description | Abstract Background Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood. Methods In this cross-sectional study, mass spectrometry was used for quantitative analysis of plasma metabolome and lipidome in 24 treatment-naïve PLWH (TNs), 33 immunological responders (IRs), 35 immunological non-responders (INRs), and 16 healthy controls (HCs). The data were analyzed using the Mann–Whitney U-test, Kruskal–Wallis test, Spearman correlation, and LASSO regression analysis. Results Significant metabolic dysregulation was observed in TNs, IRs and INRs compared to HCs. In TNs, metabolomic analysis revealed increased levels of 3-hydroxyoctanoic acid, 3-oxododecanoic acid, 5-hydroxy-L-tryptophan, 5-hydroxyindoleacetic acid, L-kynurenine, oleoylcarnitine, and pseudouridine that were positively correlated with CD8 T cell activation and inflammation-related markers, and decreased levels of phosphorylcholine, ribothymidine, and thymine that were negatively correlated. Notably, 3-hydroxyoctanoic acid and thymine were consistently associated with CD4 T cell counts and inflammation-related markers in PLWH, regardless of ART. Pathway analysis uncovered the biosynthesis of unsaturated fatty acids as the major dysregulated pathway in TNs, IRs, and INRs, while primary bile acid biosynthesis was the dysregulated pathway specifically in INRs. Lipidomic analysis indicated higher plasma triacylglycerols, free fatty acids, ceramide, and monosialodihexosyl gangliosides (GM3) in TNs, IRs, and INRs compared to HCs. Pathway enrichment and differential correlation analyses underscore perturbed systemic lipid metabolism in treatment response to ART, possibly mediated by host-commensal metabolic interactions. Ultimately, we identified two panels, one consisting of 9 metabolites and another of 8 lipids, that can effectively distinguish INRs from IRs. Conclusions Metabolic aberrations induced by chronic HIV-1 infection persist and do not recover with ART. Abnormal primary bile acid biosynthesis pathway and levels of DHA-containing lipids are closely associated with CD4 T cell recovery. These finding provide new intervention targets to achieve better immune recovery in PLWH. |
| format | Article |
| id | doaj-art-623ecf20e92346b481080b3fb5b5790f |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-623ecf20e92346b481080b3fb5b5790f2025-02-02T12:40:33ZengBMCJournal of Translational Medicine1479-58762025-01-0123111410.1186/s12967-025-06168-0Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1Lin-Yu Wan0Sin Man Lam1Hui-Huang Huang2Wen-Jing Cao3Xiang-Yi Cao4Xue-Meng Li5Li-Ping Zhang6Jia-Min Gao7Chao Zhang8Xing Fan9Yan-Mei Jiao10Guanghou Shui11Fu-Sheng Wang12Jin-Wen Song13The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesAbstract Background Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood. Methods In this cross-sectional study, mass spectrometry was used for quantitative analysis of plasma metabolome and lipidome in 24 treatment-naïve PLWH (TNs), 33 immunological responders (IRs), 35 immunological non-responders (INRs), and 16 healthy controls (HCs). The data were analyzed using the Mann–Whitney U-test, Kruskal–Wallis test, Spearman correlation, and LASSO regression analysis. Results Significant metabolic dysregulation was observed in TNs, IRs and INRs compared to HCs. In TNs, metabolomic analysis revealed increased levels of 3-hydroxyoctanoic acid, 3-oxododecanoic acid, 5-hydroxy-L-tryptophan, 5-hydroxyindoleacetic acid, L-kynurenine, oleoylcarnitine, and pseudouridine that were positively correlated with CD8 T cell activation and inflammation-related markers, and decreased levels of phosphorylcholine, ribothymidine, and thymine that were negatively correlated. Notably, 3-hydroxyoctanoic acid and thymine were consistently associated with CD4 T cell counts and inflammation-related markers in PLWH, regardless of ART. Pathway analysis uncovered the biosynthesis of unsaturated fatty acids as the major dysregulated pathway in TNs, IRs, and INRs, while primary bile acid biosynthesis was the dysregulated pathway specifically in INRs. Lipidomic analysis indicated higher plasma triacylglycerols, free fatty acids, ceramide, and monosialodihexosyl gangliosides (GM3) in TNs, IRs, and INRs compared to HCs. Pathway enrichment and differential correlation analyses underscore perturbed systemic lipid metabolism in treatment response to ART, possibly mediated by host-commensal metabolic interactions. Ultimately, we identified two panels, one consisting of 9 metabolites and another of 8 lipids, that can effectively distinguish INRs from IRs. Conclusions Metabolic aberrations induced by chronic HIV-1 infection persist and do not recover with ART. Abnormal primary bile acid biosynthesis pathway and levels of DHA-containing lipids are closely associated with CD4 T cell recovery. These finding provide new intervention targets to achieve better immune recovery in PLWH.https://doi.org/10.1186/s12967-025-06168-0HIV-1Immune recoveryMetabolomeLipidome |
| spellingShingle | Lin-Yu Wan Sin Man Lam Hui-Huang Huang Wen-Jing Cao Xiang-Yi Cao Xue-Meng Li Li-Ping Zhang Jia-Min Gao Chao Zhang Xing Fan Yan-Mei Jiao Guanghou Shui Fu-Sheng Wang Jin-Wen Song Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 Journal of Translational Medicine HIV-1 Immune recovery Metabolome Lipidome |
| title | Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 |
| title_full | Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 |
| title_fullStr | Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 |
| title_full_unstemmed | Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 |
| title_short | Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1 |
| title_sort | multi omics dissection of metabolic dysregulation associated with immune recovery in people living with hiv 1 |
| topic | HIV-1 Immune recovery Metabolome Lipidome |
| url | https://doi.org/10.1186/s12967-025-06168-0 |
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