NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome
Abstract Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway obstruction and inflammation. Non-typeable Haemophilus influenzae (NTHi) lung infections are common in COPD, promoting frequent exacerbations and accelerated lung function decline. The relationshi...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12931-025-03113-z |
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| author | Vancheswaran Gopalakrishnan Ben Sparklin Jung Hwan Kim Jerome Bouquet Margaret Kehl Tara Kenny Christopher Morehouse Carolina Caceres Paul Warrener Ventzislava A. Hristova Susan Wilson Harini Shandilya Arnita Barnes Alexey Ruzin Junmin Wang Lisa Oberg Bastian Angermann Christopher McCrae Adam Platt Daniel Muthas Sonja Hess Christine Tkaczyk Bret R. Sellman Kristoffer Ostridge Maria G. Belvisi Tom M. A. Wilkinson Karl J. Staples Antonio DiGiandomenico on behalf of the MICA II Study Group |
| author_facet | Vancheswaran Gopalakrishnan Ben Sparklin Jung Hwan Kim Jerome Bouquet Margaret Kehl Tara Kenny Christopher Morehouse Carolina Caceres Paul Warrener Ventzislava A. Hristova Susan Wilson Harini Shandilya Arnita Barnes Alexey Ruzin Junmin Wang Lisa Oberg Bastian Angermann Christopher McCrae Adam Platt Daniel Muthas Sonja Hess Christine Tkaczyk Bret R. Sellman Kristoffer Ostridge Maria G. Belvisi Tom M. A. Wilkinson Karl J. Staples Antonio DiGiandomenico on behalf of the MICA II Study Group |
| author_sort | Vancheswaran Gopalakrishnan |
| collection | DOAJ |
| description | Abstract Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway obstruction and inflammation. Non-typeable Haemophilus influenzae (NTHi) lung infections are common in COPD, promoting frequent exacerbations and accelerated lung function decline. The relationship with immune responses and NTHi are poorly understood. Herein, we comprehensively characterized the respiratory microbiome and mycobiome of patients while investigating microbial dynamics and host immune changes attributable to NTHi killing activity. Mild-to-moderate COPD patients encompassing frequent and infrequent exacerbators and healthy volunteers (HV) were enrolled. Microbial composition, proteomics and NTHi killing activity was analyzed using bronchoalveolar lavage fluid (BALF). In addition, antigen–antibody titers in sera to COPD pathogens were determined using a multiplex assay. Differential abundance analysis revealed an enrichment of Actinobacteria and Bacteroidetes in the BALF of COPD and HV subjects respectively. Significant differences in the IgA titer response were observed against NTHi antigens in COPD vs. HV. Notably, there was also significantly greater killing activity against NTHi in BALF from COPD vs. HV subjects (OR = 5.64; 95% CI = 1.75–20.20; p = 0.001). Stratification of COPD patients by NTHi killing activity identified unique microbial and protein signatures wherein Firmicutes, Actinobacteria and haptoglobin were enriched in patients with killing activity. We report that differences in host immune responses and NTHi-killing activity are associated with microbiome changes in mild-to-moderate COPD. This is suggestive of a potential link between the respiratory microbiome and immune activity against NTHi in the context of COPD pathogenesis even at this disease stage. |
| format | Article |
| id | doaj-art-66df4c363f06439bb9e6da7ed1c691a7 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-66df4c363f06439bb9e6da7ed1c691a72025-02-02T12:38:01ZengBMCRespiratory Research1465-993X2025-01-0126111410.1186/s12931-025-03113-zNTHi killing activity is reduced in COPD patients and is associated with a differential microbiomeVancheswaran Gopalakrishnan0Ben Sparklin1Jung Hwan Kim2Jerome Bouquet3Margaret Kehl4Tara Kenny5Christopher Morehouse6Carolina Caceres7Paul Warrener8Ventzislava A. Hristova9Susan Wilson10Harini Shandilya11Arnita Barnes12Alexey Ruzin13Junmin Wang14Lisa Oberg15Bastian Angermann16Christopher McCrae17Adam Platt18Daniel Muthas19Sonja Hess20Christine Tkaczyk21Bret R. Sellman22Kristoffer Ostridge23Maria G. Belvisi24Tom M. A. Wilkinson25Karl J. Staples26Antonio DiGiandomenico27on behalf of the MICA II Study GroupBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaVirology and Vaccine Discovery, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Scientific Management, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaDynamic Omics, Centre for Genomics Research (CGR), Discovery Sciences, BioPharmaceuticals R&D, AstraZenecaBiologics Engineering, Oncology R&D, AstraZenecaBiologics Engineering, Oncology R&D, AstraZenecaBiologics Engineering, Oncology R&D, AstraZenecaTranslational Scientific Management, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaQuantitative Biology, Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaVP and Head of Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaDynamic Omics, Centre for Genomics Research (CGR), Discovery Sciences, BioPharmaceuticals R&D, AstraZenecaMicrobial Antibodies and Technologies, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZenecaSVP and Head of Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZenecaClinical & Experimental Sciences, University of Southampton Faculty of MedicineClinical & Experimental Sciences, University of Southampton Faculty of MedicineMicrobial Antibodies and Technologies, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZenecaAbstract Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway obstruction and inflammation. Non-typeable Haemophilus influenzae (NTHi) lung infections are common in COPD, promoting frequent exacerbations and accelerated lung function decline. The relationship with immune responses and NTHi are poorly understood. Herein, we comprehensively characterized the respiratory microbiome and mycobiome of patients while investigating microbial dynamics and host immune changes attributable to NTHi killing activity. Mild-to-moderate COPD patients encompassing frequent and infrequent exacerbators and healthy volunteers (HV) were enrolled. Microbial composition, proteomics and NTHi killing activity was analyzed using bronchoalveolar lavage fluid (BALF). In addition, antigen–antibody titers in sera to COPD pathogens were determined using a multiplex assay. Differential abundance analysis revealed an enrichment of Actinobacteria and Bacteroidetes in the BALF of COPD and HV subjects respectively. Significant differences in the IgA titer response were observed against NTHi antigens in COPD vs. HV. Notably, there was also significantly greater killing activity against NTHi in BALF from COPD vs. HV subjects (OR = 5.64; 95% CI = 1.75–20.20; p = 0.001). Stratification of COPD patients by NTHi killing activity identified unique microbial and protein signatures wherein Firmicutes, Actinobacteria and haptoglobin were enriched in patients with killing activity. We report that differences in host immune responses and NTHi-killing activity are associated with microbiome changes in mild-to-moderate COPD. This is suggestive of a potential link between the respiratory microbiome and immune activity against NTHi in the context of COPD pathogenesis even at this disease stage.https://doi.org/10.1186/s12931-025-03113-zCOPDNon-typeable Haemophilus influenzaeMicrobiomeExacerbations |
| spellingShingle | Vancheswaran Gopalakrishnan Ben Sparklin Jung Hwan Kim Jerome Bouquet Margaret Kehl Tara Kenny Christopher Morehouse Carolina Caceres Paul Warrener Ventzislava A. Hristova Susan Wilson Harini Shandilya Arnita Barnes Alexey Ruzin Junmin Wang Lisa Oberg Bastian Angermann Christopher McCrae Adam Platt Daniel Muthas Sonja Hess Christine Tkaczyk Bret R. Sellman Kristoffer Ostridge Maria G. Belvisi Tom M. A. Wilkinson Karl J. Staples Antonio DiGiandomenico on behalf of the MICA II Study Group NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome Respiratory Research COPD Non-typeable Haemophilus influenzae Microbiome Exacerbations |
| title | NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome |
| title_full | NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome |
| title_fullStr | NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome |
| title_full_unstemmed | NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome |
| title_short | NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome |
| title_sort | nthi killing activity is reduced in copd patients and is associated with a differential microbiome |
| topic | COPD Non-typeable Haemophilus influenzae Microbiome Exacerbations |
| url | https://doi.org/10.1186/s12931-025-03113-z |
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