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Microbial ecological instability and non-linear host interactions shape airway inflammation in HIV-associated COPD

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Item Type:Article
Title:Microbial ecological instability and non-linear host interactions shape airway inflammation in HIV-associated COPD
Creators: Kayongo, Alex ORCID logoORCID: https://orcid.org/0000-0002-5338-3821, Bartolomaeus, Theda Ulrike Patricia ORCID logoORCID: https://orcid.org/0000-0002-5156-7184, Hecker, Julia, Birkner, Till ORCID logoORCID: https://orcid.org/0000-0003-2656-2821, Vila, Eremire, Ntayi, Moses Levi, Markó, Lajos ORCID logoORCID: https://orcid.org/0000-0003-1888-5575, Löber, Ulrike ORCID logoORCID: https://orcid.org/0000-0001-7468-9531, Olweny, Geoffrey ORCID logoORCID: https://orcid.org/0009-0001-8447-8479, Kyalo, Edward ORCID logoORCID: https://orcid.org/0000-0002-5162-3924, Kyamulabi, Daisy, Ndawula, Josephine, Ssengooba, Willy ORCID logoORCID: https://orcid.org/0000-0002-1643-110X, Nabatanzi, Rose, Kyobe, Samuel ORCID logoORCID: https://orcid.org/0000-0003-0444-5608, Nassali, Faith, Kigozi, Edgar, Kalyesubula, Robert ORCID logoORCID: https://orcid.org/0000-0003-3211-163X, Munana, Richard, Namaganda, Jesca, Musiime, Caroline J., Sekibira, Rogers, Bagaya, Bernard S., Kateete, David P., Joloba, Moses L., Jjingo, Daudi, Lusiba, John, Worodria, William, Mayanja-Kizza, Harriet ORCID logoORCID: https://orcid.org/0000-0002-9297-6208, Lalitha, Rejani, Ham, Wasswa, Sanyu, Ingvar ORCID logoORCID: https://orcid.org/0000-0001-5324-5448, Zawedde, Josephine, Robertson, Nicole M., Obondo, James Sande, Weidinger, Carl ORCID logoORCID: https://orcid.org/0000-0002-9948-0088, Kunkel, Desiree ORCID logoORCID: https://orcid.org/0000-0002-0054-955X, Kirenga, Bruce J. ORCID logoORCID: https://orcid.org/0000-0002-2023-2840, Siddharthan, Trishul ORCID logoORCID: https://orcid.org/0000-0001-9914-1839, Hurst, John R., Checkley, William ORCID logoORCID: https://orcid.org/0000-0003-1106-8812, Cookson, William B. ORCID logoORCID: https://orcid.org/0000-0001-9551-4677, Moffatt, Miriam F. ORCID logoORCID: https://orcid.org/0000-0001-7623-5840 and Forslund-Startceva, Sofia K. ORCID logoORCID: https://orcid.org/0000-0003-4285-6993
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.
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Date:6 October 2026
Official Publication:https://doi.org/10.1038/s41467-026-78400-4
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