Introduction

Mycobacterium tuberculosis complex (Mtbc) bacteria causing tuberculosis (TB) are among the leading infectious killers worldwide. Additionally, opportunistic non-tuberculous mycobacteria (NTMs) can cause severe respiratory infections in patients with pre-existing lung conditions. Yet, it is unclear if the lung microbiome is a risk factor to develop active TB and NTM lung disease or influences treatment outcomes.

Goals

We sought to contrast the lung microbiome of TB, and NTM patients, and identify key taxa associated with disease states.

Materials & Methods

We profiled the lung microbiomes of 23 TB, 19 NTM, and 4 non-infectious lung disease patients prior their main therapy by analyzing bronchoalveolar lavage fluid (BALFs) collected at the Research Center Borstel, Germany over 14 years. We depleted human cells and extracellular DNA, and profiled the microbiome using 16S rRNA amplicon- and exploratory whole metagenome sequencing following state-of-the-art laboratory, and analytical protocols designed for low biomass specimens.

Results

We found that the genus Serratia strongly dominates the lung microbiome of TB, and NTM patients. At the sub-genus level, we find that i) TB patients harbor higher community diversity, ii) two distinct Serratia traits are significantly associated to TB patients, one of which belongs to Serrartia grimesii as disclosed by exploratory metagenomic analysis, iii) disease state significantly influences microbiome community structure.

Summary

Serratia sp. plays a pivotal role for our understanding of microbial interactions in the lung microbiome of patients infected with Mtbc and NTMs. Future studies investigating the mechanisms of Serratia-Mycobacterium interactions and their impact on disease progression and therapy outcome are warranted.