Microbial ecological instability and non-linear host interactions shape airway inflammation in HIV-associated COPD
Abstract Chronic obstructive pulmonary disease (COPD) is increasingly recognized among people living with HIV in sub-Saharan Africa, yet the mechanisms linking airway microbial ecology to chronic inflammation remain poorly understood. Here, we study 200 adults stratified by HIV and COPD status, including 160 participants with two-year longitudinal follow-up, using an integrated multi-omics framework combining sputum 16S rRNA profiling, bacterial outer membrane vesicle quantification, airway cytokine profiling, CyTOF immune phenotyping, bulk transcriptomics of induced sputum, bronchoalveolar lavage and peripheral blood, and bronchoalveolar lavage single-cell RNA sequencing-guided deconvolution. We find that sputum microbial communities are shaped predominantly by temporal ecological turnover rather than HIV or COPD status. Although microbial diversity, microbiome instability, outer membrane vesicle burden and inferred airway cellular composition remain largely preserved, HIV-associated COPD exhibits disease-specific microbial signatures together with inflammatory transcriptional remodeling concentrated in induced sputum. Integrated analyses identify selective host-microbe interaction networks linking discrete microbial taxa with inflammatory, immune and transcriptional programmes.
Authors
- Edgar Kigozi
- William Cookson (ORCID: https://orcid.org/0000-0001-9551-4677)
- Désirée Kunkel (ORCID: https://orcid.org/0000-0002-0054-955X)
- Theda Ulrike Patricia Bartolomaeus (ORCID: https://orcid.org/0000-0002-5156-7184)
- Richard Munana (ORCID: https://orcid.org/0000-0002-9637-6189)
- Julia Hecker
- John Lusiba
- Josephine Zawedde
- Bernard S. Bagaya (ORCID: https://orcid.org/0000-0002-3847-2615)
- William Checkley (ORCID: https://orcid.org/0000-0003-1106-8812)
- Alex Kayongo (ORCID: https://orcid.org/0000-0002-5338-3821)
- Edward Kyalo (ORCID: https://orcid.org/0000-0002-5162-3924)
- Carl Weidinger (ORCID: https://orcid.org/0000-0002-9948-0088)
- Robert Kalyesubula (ORCID: https://orcid.org/0000-0003-3211-163X)
- Willy Ssengooba (ORCID: https://orcid.org/0000-0002-1643-110X)
- William O. Worodria (ORCID: https://orcid.org/0000-0002-8531-5567)
- Sofia Kirke Forslund (ORCID: https://orcid.org/0000-0003-4285-6993)
- Daudi Jjingo (ORCID: https://orcid.org/0000-0003-1685-9234)
- David Patrick Kateete (ORCID: https://orcid.org/0000-0001-8075-3069)
- Harriet Mayanja‐Kizza (ORCID: https://orcid.org/0000-0002-9297-6208)
- Nicole M. Robertson (ORCID: https://orcid.org/0000-0003-2139-8321)
- Miriam F. Moffatt (ORCID: https://orcid.org/0000-0001-7623-5840)
- Lajos Markó (ORCID: https://orcid.org/0000-0003-1888-5575)
- Samuel Kyobe (ORCID: https://orcid.org/0000-0003-0444-5608)
- Rogers Sekibira
- Ulrike Löber (ORCID: https://orcid.org/0000-0001-7468-9531)
- Bruce Kirenga (ORCID: https://orcid.org/0000-0002-2023-2840)
- Moses Lutaakome Joloba (ORCID: https://orcid.org/0000-0002-0334-9983)
- Till Birkner (ORCID: https://orcid.org/0000-0003-2656-2821)
- Faith Nassali
- Trishul Siddharthan (ORCID: https://orcid.org/0000-0001-9914-1839)
- Moses Levi Ntayi (ORCID: https://orcid.org/0000-0002-1595-2587)
- Josephine Caren Ndawula
- Rose Nabatanzi (ORCID: https://orcid.org/0000-0002-7033-2241)
- Ingvar Sanyu (ORCID: https://orcid.org/0000-0001-5324-5448)
- James Sande Obondo
- Geofrey Olweny (ORCID: https://orcid.org/0009-0001-8447-8479)
- John R Hurst (ORCID: https://orcid.org/0000-0002-7246-6040)
- Jesca Namaganda
- Rejani Lalitha
- Daisy Kyamulabi
- Wasswa Ham
- Eremire Vila
- Caroline J. Musiime
Institutions
- Austrian Academy of Sciences (AT)
- Johns Hopkins University (US)
- University of Miami (US)
- Medical University of Graz (AT)
- Max Delbrück Center (DE)
- Africa Center (US)
- Humboldt-Universität zu Berlin (DE)
- Lung Institute (US)
- Infectious Diseases Institute (UG)
- Infectious Diseases Research Collaboration (UG)
- German Centre for Cardiovascular Research (DE)
- CeMM Research Center for Molecular Medicine (AT)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- University College London (GB)
- Makerere University (UG)
- Medical University of Vienna (AT)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-06
- DOI
- https://doi.org/10.1038/s41467-026-78400-4
- Primary Topic
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- National Institutes of Health
- Fogarty International Center