The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy
ABSTRACT The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it s...
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American Society for Microbiology
2025-08-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02205-24 |
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| author | Oumar Dolo Fousseini Coulibaly Anou M. Somboro Shan Sun Modibo Diarra Aminata Maiga Soungou Bore Djeneba B. Fofana Anne-Genevieve Marcelin Brehima Diakite Yaya Kassogue Jane L. Holl Vincent Calvez Cheick B. Traoré Robert Murphy Anthony A. Fodor Mamoudou Maiga Almoustapha I. Maiga |
| author_facet | Oumar Dolo Fousseini Coulibaly Anou M. Somboro Shan Sun Modibo Diarra Aminata Maiga Soungou Bore Djeneba B. Fofana Anne-Genevieve Marcelin Brehima Diakite Yaya Kassogue Jane L. Holl Vincent Calvez Cheick B. Traoré Robert Murphy Anthony A. Fodor Mamoudou Maiga Almoustapha I. Maiga |
| author_sort | Oumar Dolo |
| collection | DOAJ |
| description | ABSTRACT The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to 6 and 12 months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants’ intestinal microbial structures and derived metabolic pathways. Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in Proteobacteria at 6 months of ART, continuing until 12 months of ART. Lower proportions of Bacteroidetes were noted pre-ART, but they increased slightly at 6 months of ART before decreasing again at 12 months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after 12 months of ART, and this mechanism was correlated with a decrease in Ruminococcus bromii species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.IMPORTANCEResearchers are facing a major challenge in the treatment of HIV infection due to the continuous use of antiretroviral (ARV) molecules. However, regularly monitoring these molecules is necessary because they are not without consequences. They have toxicity and side effects and could also destabilize the intestinal microbiota, which could harm the metabolic pathways essential to good health. This study reveals that ARV treatment only partially restores gut microbiota dysbiosis and alters metabolic pathways due to pathogenic taxa. This provides additional insights into the relationship between antiretroviral therapy and the microbiome, potentially leading to new prevention and treatment strategies such as probiotic/prebiotic or microbiota transplants. |
| format | Article |
| id | doaj-art-ddb89ce643e04ee7bfb53a5404dadcc1 |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-ddb89ce643e04ee7bfb53a5404dadcc12025-08-20T03:38:59ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.02205-24The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapyOumar Dolo0Fousseini Coulibaly1Anou M. Somboro2Shan Sun3Modibo Diarra4Aminata Maiga5Soungou Bore6Djeneba B. Fofana7Anne-Genevieve Marcelin8Brehima Diakite9Yaya Kassogue10Jane L. Holl11Vincent Calvez12Cheick B. Traoré13Robert Murphy14Anthony A. Fodor15Mamoudou Maiga16Almoustapha I. Maiga17University Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliMedical Biology Laboratory of the Point G University Hospital Center, Bamako, Bamako Capital District, MaliUniversity Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliDepartment of Bioinformatics, University of North Carolina at Charlotte, Charlotte, North Carolina, USAResearch and Training Center for Molecular Pathologies (CREFPAM), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliMedical Biology Laboratory of the Point G University Hospital Center, Bamako, Bamako Capital District, MaliResearch and Training Center for Molecular Pathologies (CREFPAM), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliUniversity Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliVirology Department of the “Pitié-Salpêtrière” Hospital, Paris, FranceResearch and Training Center for Molecular Pathologies (CREFPAM), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliResearch and Training Center for Molecular Pathologies (CREFPAM), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliDepartment of Neurology, University of Chicago, Chicago, Illinois, USAVirology Department of the “Pitié-Salpêtrière” Hospital, Paris, FranceResearch and Training Center for Molecular Pathologies (CREFPAM), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliInstitute for Global Health, Northwestern University, Evanston, Illinois, USADepartment of Bioinformatics, University of North Carolina at Charlotte, Charlotte, North Carolina, USAUniversity Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliUniversity Clinical Research Center (UCRC), University of Sciences, Techniques and Technologies of Bamako, Bamako, Bamako Capital District, MaliABSTRACT The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to 6 and 12 months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants’ intestinal microbial structures and derived metabolic pathways. Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in Proteobacteria at 6 months of ART, continuing until 12 months of ART. Lower proportions of Bacteroidetes were noted pre-ART, but they increased slightly at 6 months of ART before decreasing again at 12 months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after 12 months of ART, and this mechanism was correlated with a decrease in Ruminococcus bromii species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.IMPORTANCEResearchers are facing a major challenge in the treatment of HIV infection due to the continuous use of antiretroviral (ARV) molecules. However, regularly monitoring these molecules is necessary because they are not without consequences. They have toxicity and side effects and could also destabilize the intestinal microbiota, which could harm the metabolic pathways essential to good health. This study reveals that ARV treatment only partially restores gut microbiota dysbiosis and alters metabolic pathways due to pathogenic taxa. This provides additional insights into the relationship between antiretroviral therapy and the microbiome, potentially leading to new prevention and treatment strategies such as probiotic/prebiotic or microbiota transplants.https://journals.asm.org/doi/10.1128/spectrum.02205-24antiretroviral therapygut microbiotaHIVMali |
| spellingShingle | Oumar Dolo Fousseini Coulibaly Anou M. Somboro Shan Sun Modibo Diarra Aminata Maiga Soungou Bore Djeneba B. Fofana Anne-Genevieve Marcelin Brehima Diakite Yaya Kassogue Jane L. Holl Vincent Calvez Cheick B. Traoré Robert Murphy Anthony A. Fodor Mamoudou Maiga Almoustapha I. Maiga The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy Microbiology Spectrum antiretroviral therapy gut microbiota HIV Mali |
| title | The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy |
| title_full | The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy |
| title_fullStr | The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy |
| title_full_unstemmed | The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy |
| title_short | The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy |
| title_sort | human gut microbiome and its metabolic pathway dynamics before and during hiv antiretroviral therapy |
| topic | antiretroviral therapy gut microbiota HIV Mali |
| url | https://journals.asm.org/doi/10.1128/spectrum.02205-24 |
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