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. 2025 Jun 10:16:1555441.
doi: 10.3389/fimmu.2025.1555441. eCollection 2025.

Microbiome profiling reveals gut bacterial species associated with rapid lung function decline in people with HIV

Xiangning Bai  1   2   3 , Sajan C Raju  3   4 , Andreas Dehlbæk Knudsen  5 , Rebekka Faber Thudium  5 , Nicoline Stender Arentoft  5 , Marco Gelpi  5   6 , Safura-Luise Heidari  5 , Ken M Kunisaki  7   8 , Karsten Kristiansen  9   10 , Johannes Roksund Hov  3   11 , Susanne Dam Nielsen  5   12   13 , Marius Trøseid  3   4   14
Affiliations

Microbiome profiling reveals gut bacterial species associated with rapid lung function decline in people with HIV

Xiangning Bai et al. Front Immunol. .

Abstract

Background: People with HIV (PWH) have an increased risk of pulmonary comorbidities compared to people without HIV. The gut microbiome regulates host immunity and is altered in PWH. This study aims to determine potential associations between gut microbiome, lung function decline, and airflow limitation in PWH.

Methods: PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study with available lung function testing and microbiome data were included (n=385). The gut microbiome was characterized using shotgun metagenomic sequencing. Associations between gut microbiome, rapid lung function decline, and airflow limitation were analysed in multivariable logistic regressions adjusted for traditional and HIV-associated risk factors for lung disease.

Results: Several bacterial species were significantly enriched in PWH with rapid lung function decline, including opportunistic pathogenic bacterial species Bacteroides coprophilus, Klebsiella michiganensis, and Clostridium perfringens. A gut microbial dysbiosis index based on compositional changes was associated with rapid lung function decline (adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) [1.11-1.27], p<0.001), and airflow limitation (aOR 1.16, 95% CI [1.04-1.29], p=0.007) in adjusted multivariable logistic regression analyses.

Conclusion: Associations between the gut dysbiosis index and rapid lung function decline and airflow limitation suggest a potential role of certain gut bacterial species in the pathogenesis of pulmonary comorbidities in PWH.

Keywords: HIV; airflow limitation; gut microbiome; lung function decline; pulmonary comorbidity; spirometry.

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Conflict of interest statement

AK reports grants from the European Commission EU 7th Framework Grant ID:603266, Gilead Sciences Research Scholars Program 2023 and a speaker’s fee from GlaxoSmithKline’; his wife is employed at Novo Nordisk. RT reports a travel grant from Gilead Sciences. NA reports PhD grant from the Research Foundation of Odense University Hospital and Copenhagen University Hospital Rigshospitalet. S-LH reports a research-scholar grant from the Novo Nordic Foundation and a travel grant from GlaxoSmithKline. KMK reports personal fees from Nuvaira for Data and Safety Monitoring Board work. SN reports unrestricted research grants from Novo Nordic Foundation, Rigshospitalet Research Foundation, Independent Research Fund Denmark, Svend Andersen Fonden; she is on advisory board for Gilead, Takeda, and GSK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Gut microbiome profiles at species level in PWH with and without rapid lung function decline. (A), Shannon diversity index. (B), inverse Simpson diversity index. (C), Beta-diversity assessed by the Bray–Curtis dissimilarity index, visualized using Principal Coordinate Analysis (PCoA). (D), Bacterial species differentially abundant between PWH with and without rapid lung function decline, analyzed using the DESeq2 package, adjusted for smoking.
See this image and copyright information in PMC

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