Nontuberculous mycobacterial (NTM) pulmonary
infections in people with
cystic fibrosis (CF) are associated with significant morbidity and mortality and are increasing in prevalence. Host risk factors for NTM
infection in CF are largely unknown. We hypothesize that the airway microbiota represents a host risk factor for NTM
infection. In this study, 69 sputum samples were collected from 59 people with CF; 42 samples from 32 subjects with NTM
infection (14 samples collected before incident NTM
infection and 28 samples collected following incident NTM
infection) were compared to 27 samples from 27 subjects without NTM
infection. Sputum samples were analyzed with
16S rRNA gene sequencing and metabolomics. A supervised classification and correlation analysis framework (sparse partial least-squares discriminant analysis [sPLS-DA]) was used to identify correlations between the microbial and metabolomic profiles of the NTM cases compared to the NTM-negative controls. Several metabolites significantly differed in the NTM cases compared to controls, including decreased levels of
tryptophan-associated and
branched-chain amino acid metabolites, while compounds involved in
phospholipid metabolism displayed increased levels. When the metabolome and microbiome data were integrated by sPLS-DA, the models and component ordinations showed separation between the NTM and control samples. While this study could not determine if the observed differences in sputum metabolites between the cohorts reflect metabolic changes that occurred as a result of the NTM
infection or metabolic features that contributed to NTM acquisition, it is hypothesis generating for future work to investigate host and bacterial community factors that may contribute to NTM
infection risk in CF. IMPORTANCE Host risk factors for nontuberculous mycobacterial (NTM)
infection in people with
cystic fibrosis (CF) are largely unclear. The goal of this study was to help identify potential host and bacterial community risk factors for NTM
infection in people with CF, using microbiome and metabolome data from CF sputum samples. The data obtained in this study identified several metabolic profile differences in sputum associated with NTM
infection in CF, including 2-methylcitrate/
homocitrate and selected
ceramides. These findings represent potential risk factors and therapeutic targets for preventing and/or treating NTM
infections in people with CF.