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Gut virome alterations in patients with chronic obstructive pulmonary disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage, Myoviridae sp., and Synechococcus phage, showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD.

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Previous studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD.

SUBMITTER: Liu Y

PROVIDER: S-EPMC11218493 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Gut virome alterations in patients with chronic obstructive pulmonary disease.

Liu Yue Y Huang Qingsong Q Zhuang Zhenhua Z Yang Hongjing H Gou Xiaoling X Xu Tong T Liu Ke K Wang Jun J Liu Bo B Gao Peiyang P Cao Feng F Yang Bin B Zhang Chuantao C Chen Mei M Fan Gang G

Microbiology spectrum 20240524 7

Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial ...[more]

PMID: 38785444

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Project description:BackgroundMetabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.MethodsPBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs' cycle substrate) was measured using the XFp Extracellular Flux Analyzer. Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry. RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied. Patient's data was analyzed using the Mann Whitney U test, whereas Student's t test was performed to analyze the in-vitro data.ResultsPBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%). Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV1 (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed. The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α. In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate.ConclusionsThese findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease.Trial registrationThis observational study was retrospectively registered in the Clinical Trails Registry - India (ICMR - NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441 .

Project description:BACKGROUND:Adenosine is generated in response to cellular stress and damage and is elevated in the lungs of patients with chronic lung disease. Adenosine signaling through its cell surface receptors serves as an amplifier of chronic lung disorders, suggesting adenosine-based therapeutics may be beneficial in the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Previous studies in mouse models of chronic lung disease demonstrate that the key components of adenosine metabolism and signaling are altered. Changes include an up-regulation of CD73, the major enzyme of adenosine production and down-regulation of adenosine deaminase (ADA), the major enzyme for adenosine metabolism. In addition, adenosine receptors are elevated. METHODOLOGY/PRINCIPAL FINDINGS:The focus of this study was to utilize tissues from patients with COPD or IPF to examine whether changes in purinergic metabolism and signaling occur in human disease. Results demonstrate that the levels of CD73 and A(2B)R are elevated in surgical lung biopsies from severe COPD and IPF patients. Immunolocalization assays revealed abundant expression of CD73 and the A(2B)R in alternatively activated macrophages in both COPD and IPF samples. In addition, mediators that are regulated by the A(2B)R, such as IL-6, IL-8 and osteopontin were elevated in these samples and activation of the A(2B)R on cells isolated from the airways of COPD and IPF patients was shown to directly induce the production of these mediators. CONCLUSIONS/SIGNIFICANCE:These findings suggest that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of patients with COPD and IPF, and provide proof of concept information that these disorders may benefit from adenosine-based therapeutics. Furthermore, this study provides the first evidence that A(2B)R signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders.

Dataset Information

Gut virome alterations in patients with chronic obstructive pulmonary disease.

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Gut virome alterations in patients with chronic obstructive pulmonary disease.

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