학술논문

Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection.
Document Type
Academic Journal
Author
Kayongo A; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Bartolomaeus TUP; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; German Centre for Cardiovascular Research, Berlin, Germany.; Birkner T; Experimental and Clinical Research Center, A Cooperation of Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; German Centre for Cardiovascular Research, Berlin, Germany.; Markó L; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; German Centre for Cardiovascular Research, Berlin, Germany.; Löber U; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; German Centre for Cardiovascular Research, Berlin, Germany.; Kigozi E; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Atugonza C; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Munana R; Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Mawanda D; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Sekibira R; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Uwimaana E; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Alupo P; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Kalyesubula R; African Community Center for Social Sustainability (ACCESS), Department of Research, Nakaseke, Uganda.; Makerere University, College of Health Sciences, Department of Medicine, Kampala, Uganda.; Knauf F; Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Siddharthan T; University of Miami, School of Medicine, Division of pulmonary and critical care medicine, Miami, Florida, USA.; Bagaya BS; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Kateete DP; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Joloba ML; Makerere University, College of Health Sciences, Department of Immunology and Molecular Biology, Kampala, Uganda.; Sewankambo NK; Makerere University, College of Health Sciences, Department of Medicine, Kampala, Uganda.; Jjingo D; Makerere University, College of Computing and Information Sciences, Department of Computer Science, Kampala, Uganda.; African Center of Excellence in Bioinformatics and Data Science, Infectious Diseases Institute, Kampala, Uganda.; Kirenga B; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda.; Makerere University, College of Health Sciences, Department of Medicine, Kampala, Uganda.; Checkley W; Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Center for Global Non-Communicable Disease Research and Training, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Forslund SK; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; German Centre for Cardiovascular Research, Berlin, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Source
Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
Subject
Language
English
Abstract
Sub-Saharan Africa has increased morbidity and mortality related to chronic obstructive pulmonary disease (COPD). COPD among people living with HIV (PLWH) has not been well studied in this region, where HIV/AIDS is endemic. Increasing evidence suggests that respiratory microbial composition plays a role in COPD severity. Therefore, we aimed to investigate microbiome patterns and associations among PLWH with COPD in Sub-Saharan Africa. We conducted a cross-sectional study of 200 adults stratified by HIV and COPD in rural Uganda. Induced sputum samples were collected as an easy-to-obtain proxy for the lower respiratory tract microbiota. We performed 16S rRNA gene sequencing and used PICRUSt2 (version 2.2.3) to infer the functional profiles of the microbial community. We used a statistical tool to detect changes in specific taxa that searches and adjusts for confounding factors such as antiretroviral therapy (ART), age, sex, and other participant characteristics. We could cluster the microbial community into three community types whose distribution was shown to be significantly impacted by HIV. Some genera, e.g., Veillonella , Actinomyces , Atopobium , and Filifactor , were significantly enriched in HIV-infected individuals, while the COPD status was significantly associated with Gammaproteobacteria and Selenomonas abundance. Furthermore, reduced bacterial richness and significant enrichment in Campylobacter were associated with HIV-COPD comorbidity. Functional prediction using PICRUSt2 revealed a significant depletion in glutamate degradation capacity pathways in HIV-positive patients. A comparison of our findings with an HIV cohort from the United Kingdom revealed significant differences in the sputum microbiome composition, irrespective of viral suppression. IMPORTANCE Even with ART available, HIV-infected individuals are at high risk of suffering comorbidities, as shown by the high prevalence of noninfectious lung diseases in the HIV population. Recent studies have suggested a role for the respiratory microbiota in driving chronic lung inflammation. The respiratory microbiota was significantly altered among PLWH, with disease persisting up to 3 years post-ART initiation and HIV suppression. The community structure and diversity of the sputum microbiota in COPD are associated with disease severity and clinical outcomes, both in stable COPD and during exacerbations. Therefore, a better understanding of the sputum microbiome among PLWH could improve COPD prognostic and risk stratification strategies. In this study, we observed that in a virologically suppressed HIV cohort in rural Uganda, we could show differences in sputum microbiota stratified by HIV and COPD, reduced bacterial richness, and significant enrichment in Campylobacter associated with HIV-COPD comorbidity.