Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy
Background: Antiretroviral therapy (ART) effectively reduces opportunistic infections and mortality in people living with HIV (PLWH); however, some patients exhibit poor immune recovery. This study explores the connections among immune responses, metabolites, and the gut microbiota in PLWH with diff...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Current Research in Microbial Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666517425000021 |
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| author | Xuebin Tian Zhongyao Gao Yiwen Xie Xiangyun Lu Yulong Zhao Peng Yao Mingqing Dong Lifeng Yu Nanping Wu |
| author_facet | Xuebin Tian Zhongyao Gao Yiwen Xie Xiangyun Lu Yulong Zhao Peng Yao Mingqing Dong Lifeng Yu Nanping Wu |
| author_sort | Xuebin Tian |
| collection | DOAJ |
| description | Background: Antiretroviral therapy (ART) effectively reduces opportunistic infections and mortality in people living with HIV (PLWH); however, some patients exhibit poor immune recovery. This study explores the connections among immune responses, metabolites, and the gut microbiota in PLWH with differing reactions to ART. Methods: We analyzed the gut microbiota composition, metabolites, and immune markers in 38 PLWH who showed an immunological response (IR) and 32 who did not (INR), as classified according to CD4+ T-cell levels after 24 months of ART. Additionally, in vitro assays using cell counting kit 8, flow cytometry, and quantitative real-time reverse transcription PCR were employed to assess the effects of the metabolites on cell viability, immune marker expression, and cytokine levels. Results: Gut microbiota and metabolic profiles differed significantly between the IR and INR groups. Enterococcus was more abundant in the INR group, whereas [Ruminococcus]_gnavus_group levels were reduced. Significant metabolic pathway alterations included decreased folate biosynthesis and biotin metabolism. We observed negative associations of Parabacteroides with activation markers on CD4+ T-cells, and positive correlations with CD4/CD8 ratios. Enterococcus showed inverse relationships with these markers. Indole-3-acetyl-beta-1-D-glucoside (area under the curve value = 0.8931), had the best discriminatory ability. Further experiments showed that Indole-3-acetyl-beta-1-D-glucoside significantly decreased the proportions of CD4+CD57+, effector CD4+, CD4+PD1+, CD8+CD57+, effector CD8+, and CD8+HLA-DR+ T cells. Moreover, mRNA expression analysis showed that Indole-3-acetyl-beta-1-D-glucoside treatment led to a suppression of pro-inflammatory cytokines. Conclusion: The multi-omics approach highlighted potential biomarkers for immune recovery in HIV, suggesting avenues for further research into treatment strategies. |
| format | Article |
| id | doaj-art-4b3598b3af4849fbae3e62f8b1aa6f76 |
| institution | Kabale University |
| issn | 2666-5174 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Microbial Sciences |
| spelling | doaj-art-4b3598b3af4849fbae3e62f8b1aa6f762025-01-16T04:29:18ZengElsevierCurrent Research in Microbial Sciences2666-51742025-01-018100340Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapyXuebin Tian0Zhongyao Gao1Yiwen Xie2Xiangyun Lu3Yulong Zhao4Peng Yao5Mingqing Dong6Lifeng Yu7Nanping Wu8Cell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaCollege of Life Sciences, Wuhan University, Wuhan, Hubei, ChinaCell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaShandong First Medical University, Jinan, Shandong, ChinaDepartment of Infectious Disease, Zhejiang Qingchun Hospital, Hangzhou, Zhejiang, ChinaDepartment of Infectious Disease, Zhejiang Qingchun Hospital, Hangzhou, Zhejiang, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong medicine and Health Key Laboratory of Emergency Medicine, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, Shandong, China; Corresponding author.Cell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Corresponding author.Background: Antiretroviral therapy (ART) effectively reduces opportunistic infections and mortality in people living with HIV (PLWH); however, some patients exhibit poor immune recovery. This study explores the connections among immune responses, metabolites, and the gut microbiota in PLWH with differing reactions to ART. Methods: We analyzed the gut microbiota composition, metabolites, and immune markers in 38 PLWH who showed an immunological response (IR) and 32 who did not (INR), as classified according to CD4+ T-cell levels after 24 months of ART. Additionally, in vitro assays using cell counting kit 8, flow cytometry, and quantitative real-time reverse transcription PCR were employed to assess the effects of the metabolites on cell viability, immune marker expression, and cytokine levels. Results: Gut microbiota and metabolic profiles differed significantly between the IR and INR groups. Enterococcus was more abundant in the INR group, whereas [Ruminococcus]_gnavus_group levels were reduced. Significant metabolic pathway alterations included decreased folate biosynthesis and biotin metabolism. We observed negative associations of Parabacteroides with activation markers on CD4+ T-cells, and positive correlations with CD4/CD8 ratios. Enterococcus showed inverse relationships with these markers. Indole-3-acetyl-beta-1-D-glucoside (area under the curve value = 0.8931), had the best discriminatory ability. Further experiments showed that Indole-3-acetyl-beta-1-D-glucoside significantly decreased the proportions of CD4+CD57+, effector CD4+, CD4+PD1+, CD8+CD57+, effector CD8+, and CD8+HLA-DR+ T cells. Moreover, mRNA expression analysis showed that Indole-3-acetyl-beta-1-D-glucoside treatment led to a suppression of pro-inflammatory cytokines. Conclusion: The multi-omics approach highlighted potential biomarkers for immune recovery in HIV, suggesting avenues for further research into treatment strategies.http://www.sciencedirect.com/science/article/pii/S2666517425000021Human immunodeficiency virusGut microbiotaFecal metabolitesImmunological respondersImmunological non-responders |
| spellingShingle | Xuebin Tian Zhongyao Gao Yiwen Xie Xiangyun Lu Yulong Zhao Peng Yao Mingqing Dong Lifeng Yu Nanping Wu Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy Current Research in Microbial Sciences Human immunodeficiency virus Gut microbiota Fecal metabolites Immunological responders Immunological non-responders |
| title | Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy |
| title_full | Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy |
| title_fullStr | Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy |
| title_full_unstemmed | Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy |
| title_short | Interrelationship between altered metabolites and the gut microbiota in people living with HIV with different immune responses to antiretroviral therapy |
| title_sort | interrelationship between altered metabolites and the gut microbiota in people living with hiv with different immune responses to antiretroviral therapy |
| topic | Human immunodeficiency virus Gut microbiota Fecal metabolites Immunological responders Immunological non-responders |
| url | http://www.sciencedirect.com/science/article/pii/S2666517425000021 |
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