Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status
Alex Kayongo,
Moses Levi Ntayi,
Geoffrey Olweny,
Edward Kyalo,
Josephine Ndawula,
Willy Ssengooba,
Edgar Kigozi,
Robert Kalyesubula,
Richard Munana,
Jesca Namaganda,
Musiime Caroline,
Rogers Sekibira,
Bernard Sentalo Bagaya,
David Patrick Kateete,
Moses Lutaakome Joloba,
Daudi Jjingo,
Obondo James Sande,
Harriet Mayanja-Kizza
Affiliations
Alex Kayongo
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda; Corresponding author
Moses Levi Ntayi
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda
Geoffrey Olweny
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Edward Kyalo
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda
Josephine Ndawula
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda
Willy Ssengooba
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda
Edgar Kigozi
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Robert Kalyesubula
Department of Research, African Community Center for Social Sustainability (ACCESS), Nakaseke 256, Uganda; Department of Medicine, Makerere University, College of Health Sciences, Kampala 256, Uganda
Richard Munana
Department of Research, African Community Center for Social Sustainability (ACCESS), Nakaseke 256, Uganda
Jesca Namaganda
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda; Lung Institute, Makerere University College of Health Sciences, Kampala 256, Uganda
Musiime Caroline
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Rogers Sekibira
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Bernard Sentalo Bagaya
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
David Patrick Kateete
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Moses Lutaakome Joloba
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Daudi Jjingo
College of Computing and Information Sciences, Computer Science, Makerere University, Kampala 256, Uganda; African Center of Excellence in Bioinformatics and Data Science, Infectious Diseases Institute, Kampala 256, Uganda
Obondo James Sande
Department of Immunology and Molecular Biology, Makerere University, College of Health Sciences, Kampala 256, Uganda
Harriet Mayanja-Kizza
Department of Medicine, Makerere University, College of Health Sciences, Kampala 256, Uganda
Summary: Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals.
