Non-Tuberculosis Mycobacteria Infection and The Wider Lung Microbiota in Cystic Fibrosis

Hardman, Michelle H. (2024) Non-Tuberculosis Mycobacteria Infection and The Wider Lung Microbiota in Cystic Fibrosis. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Non-tuberculosis mycobacteria (NTM) infections in people with cystic fibrosis (PWCF) pose significant challenges and can have detrimental effects on patient prognosis. This study aims to investigate the impact of NTM positivity on the background microbiome in PWCF, focusing on the culture-positive cohorts for Mycobacterium avium complex and Mycobacterium abscessus complex. Additionally, the relationship between genetic modulator status and alterations in microbial composition was examined. The study employed optimised detection methods using the Illumina MiSeq platform for NTM complexes in low-diversity samples. Furthermore, the study investigated the regulation of gene expression during CF exacerbation states and explored the effect of NTM positivity on patient factors, such as the percent predicted forced expiratory volume in one second (%FEV1). The study's findings demonstrate the optimization and improvement of NTM complex detection in low diversity samples, enabling a comprehensive evaluation of the effects of NTM positivity on the broader lung microbiota. The results indicate that the presence of NTM complexes does indeed alter the diversity and the composition of the lung microbiota in CF patients, including those taking genetic modulators. Moreover, patient factors, including NTM culture status, age, and exacerbation phases, were found to influence %FEV1. Additionally, the study observed correlations between the regulation of certain virulence factors and the patient factors: lung function, C-reactive protein levels and neutrophil counts. These findings contribute to the understanding of NTM infections in CF patients and highlight the need for further research in this area. The knowledge gained from this study has implications for improving diagnostics, treatment strategies, and patient management, ultimately aiming to enhance outcomes and prolong the lives of CF patients.