Oropharyngeal Microbial Ecosystem Perturbations Influence the Risk for Acute Respiratory Infections in Common Variable Immunodeficiency

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Jun 14

PMID 38873612

Authors

Federica Pulvirenti

Maria Giufre

Tancredi M Pentimalli

Romina Camilli

Cinzia Milito

Annalisa Villa

Eleonora Sculco

Marina Cerquetti

Annalisa Pantosti

Isabella Quinti

Affiliations

Soon will be listed here.

Abstract

Background: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited.

Objective: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections.

Methods: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients.

Results: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order , including the family . Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of and genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of and was associated with acute respiratory infections within six months.

Conclusions: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.

Citing Articles

Linking Microbiota Profiles to Disease Characterization in Common Variable Immunodeficiency: The Case of Granulomatous-Lymphocytic Interstitial Lung Disease.

Cabanero-Navalon M, Carda-Dieguez M, Moral Moral P, Mira A, Balastegui-Martin H, Salavert-Lleti M Biomedicines. 2024; 12(10).

PMID: 39457552 PMC: 11505043. DOI: 10.3390/biomedicines12102239.

References

Castagnoli R, Pala F, Bosticardo M, Licari A, Delmonte O, Villa A . Gut Microbiota-Host Interactions in Inborn Errors of Immunity. Int J Mol Sci. 2021; 22(3). PMC: 7866830. DOI: 10.3390/ijms22031416. View

Schloss P, Westcott S, Ryabin T, Hall J, Hartmann M, Hollister E . Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009; 75(23):7537-41. PMC: 2786419. DOI: 10.1128/AEM.01541-09. View

Amrouche T, Chikindas M . Probiotics for immunomodulation in prevention against respiratory viral infections with special emphasis on COVID-19. AIMS Microbiol. 2022; 8(3):338-356. PMC: 9576497. DOI: 10.3934/microbiol.2022024. View

Pathak J, Yan Y, Zhang Q, Wang L, Ge L . The role of oral microbiome in respiratory health and diseases. Respir Med. 2021; 185:106475. DOI: 10.1016/j.rmed.2021.106475. View

Tiew P, Meldrum O, Chotirmall S . Applying Next-Generation Sequencing and Multi-Omics in Chronic Obstructive Pulmonary Disease. Int J Mol Sci. 2023; 24(3). PMC: 9918109. DOI: 10.3390/ijms24032955. View

Seidel M, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J . The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract. 2019; 7(6):1763-1770. DOI: 10.1016/j.jaip.2019.02.004. View

Verma N, Grimbacher B, Hurst J . Lung disease in primary antibody deficiency. Lancet Respir Med. 2015; 3(8):651-60. DOI: 10.1016/S2213-2600(15)00202-7. View

Gomaa E . Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. 2020; 113(12):2019-2040. DOI: 10.1007/s10482-020-01474-7. View

Rofael S, Brown J, Lipman M, Lowe D, Spratt D, Quaderi S . Impact of prophylactic and 'rescue pack' antibiotics on the airway microbiome in chronic lung disease. BMJ Open Respir Res. 2023; 10(1). PMC: 10124267. DOI: 10.1136/bmjresp-2022-001335. View

10.

Yagi K, Huffnagle G, Lukacs N, Asai N . The Lung Microbiome during Health and Disease. Int J Mol Sci. 2021; 22(19). PMC: 8509400. DOI: 10.3390/ijms221910872. View

11.

Huus K, Petersen C, Finlay B . Diversity and dynamism of IgA-microbiota interactions. Nat Rev Immunol. 2021; 21(8):514-525. DOI: 10.1038/s41577-021-00506-1. View

12.

Hazime R, Eddehbi F, El Mojadili S, Lakhouaja N, Souli I, Salami A . Inborn errors of immunity and related microbiome. Front Immunol. 2022; 13:982772. PMC: 9513548. DOI: 10.3389/fimmu.2022.982772. View

13.

Yoon H, Moon S, Song J . Lung Tissue Microbiome Is Associated With Clinical Outcomes of Idiopathic Pulmonary Fibrosis. Front Med (Lausanne). 2021; 8:744523. PMC: 8559550. DOI: 10.3389/fmed.2021.744523. View

14.

McCauley K, Flynn K, Calatroni A, DiMassa V, LaMere B, Fadrosh D . Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations. J Allergy Clin Immunol. 2022; 150(1):204-213. DOI: 10.1016/j.jaci.2022.01.020. View

15.

Bunyavanich S, Shen N, Grishin A, Wood R, Burks W, Dawson P . Early-life gut microbiome composition and milk allergy resolution. J Allergy Clin Immunol. 2016; 138(4):1122-1130. PMC: 5056801. DOI: 10.1016/j.jaci.2016.03.041. View

16.

Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E . The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2007; 111(1):77-85. DOI: 10.1182/blood-2007-06-091744. View

17.

Jorgensen S, Troseid M, Kummen M, Anmarkrud J, Michelsen A, Osnes L . Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol. 2016; 9(6):1455-1465. DOI: 10.1038/mi.2016.18. View

18.

Carsetti R, Di Sabatino A, Rosado M, Cascioli S, Piano Mortari E, Milito C . Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis. Front Immunol. 2020; 10:2937. PMC: 6960143. DOI: 10.3389/fimmu.2019.02937. View

19.

Dickson R, Erb-Downward J, Huffnagle G . The role of the bacterial microbiome in lung disease. Expert Rev Respir Med. 2013; 7(3):245-57. PMC: 4007100. DOI: 10.1586/ers.13.24. View

20.

Pulvirenti F, Camilli R, Giufre M, Milito C, Pimentel de Araujo F, Mancini F . Risk factors for Haemophilus influenzae and pneumococcal respiratory tract colonization in CVID. J Allergy Clin Immunol. 2018; 142(6):1999-2002.e3. DOI: 10.1016/j.jaci.2018.08.014. View