Sputum microbiome differs in refractory, cured nontuberculosis mycobacterial lung disease

Key takeaways:

• Microbial diversity was more prevalent in patients with cured vs. treatment-resistant nontuberculosis mycobacterial lung disease.
• Species composition changed over time with antibiotic treatment.

HONOLULU — A patient’s sputum microbiome may serve as a biomarker for the outcome of antibiotic treatment for nontuberculosis mycobacterial pulmonary disease, according to research presented at the CHEST Annual Meeting.

Microbial diversity at baseline appeared higher among those who reached a microbiologic cure vs. those resistant to treatment, and both sets of patients had different species composition with time and continued treatment, according to researchers.

Noeul Kang

“While there exists a scoring system for predicting the mortality of patients with nontuberculosis mycobacterial pulmonary disease (NTM-PD) — the BACES score — currently, there is no established prediction system to ascertain treatment outcomes,” Noeul Kang, MD, clinical assistant professor at Samsung Medical Center in Seoul, told Healio. “Although several things have to be clarified, our study in part suggests that the sputum microbiome can potentially serve as an index for predicting treatment outcomes.”

Using data of 14 patients (mean age, 61 years; 12 women; 12 never smoking status) with NTM-PD who either completed antibiotic treatment or received it between 2020 and 2022, Kang and colleagues assessed two sputum samples from each patient — one taken at baseline and one at a follow-up visit —to find out how a patients’ response to treatment is reflected in their sputum microbiome.

Of the total cohort, half of the patients did not respond to treatment and still had positive cultures with causative NTM species that required them to continue treatment, whereas the remaining half achieved microbiological cure with multiple consecutive negative cultures, Kang said during her presentation.

In terms of baseline characteristics, researchers noted six patients had Mycobacterium avium complex (refractory group, n = 2, cure group, n = 4), five had M. abscessus (refractory group, n = 3; cure group, n = 2) and three patients had a mixed infection (refractory group, n = 2; cure group, n = 1).

Researchers built the microbiome library of the patients’ sputum samples using 16S rRNA gene sequencing.

Compared with the cure group, researchers found a less diverse sputum microbiome composition at baseline in refractory patients using several different measures of alpha diversity, including the ACE index (P = .025), Chao1 index (P = .035) and Jackknife (P = .048).

In terms of beta-diversity, researchers observed significant species-level differences among refractory patients when comparing their follow-up samples to samples from microbiologically cured patients at follow-up (Jensen-Shannon, PERMANOVA, P = .015).

“Traditionally, the lung was considered to be a sterile organ,” Kang told Healio. “However, recent findings suggest that the lung harbors a complex variety of microorganisms and the dysbiosis of lung microbiota is associated with several lung diseases. What’s particularly intriguing from this research is that a stable microbial environment in the lung may serve a protective function against NTM-PD.”

Notably, comparing follow-up samples between the two groups revealed that the microbiological cure group had a larger abundance of species from the Streptococcus pneumoniae (P = .016), Prevotella melaninogenica (P = .042), Fusobacterium nucleatum (P = .032), Neisseria elongate (P = .001), Haemophilus parahaemolyticus (P = .036), H. haemolyticus (P = .011) and P. denticola (P = .031) groups when using linear discriminant analysis effect sizes.

“For the microbiological cure group, we used the sputum samples of those who had successfully completed antibiotic treatment,” Kang told Healio. “Thus, it would be important to observe microbiological changes both prior to and during the antibiotic treatment, with particular attention to the changes in microbial diversity.”

Although there has been interest to study the microbiome in asthma, COPD and bronchiectasis, the same has not been the case for NTM-PD, Kang added.

“This could be attributed, in part, to the challenges posed by the nature of NTM, as it is ‘mycobacteria’ (not bacteria) and NTM-PD involves multiple antibiotic treatments, making it difficult to isolate the microbiome effects,” she said. “Nevertheless, as it remains an underexplored area, it would be highly beneficial if more respiratory researchers have interest in investigating the microbiome of NTM-PD patients.”

Reference:

• Comparison of sputum microbiome diversities in patients with nontuberculous mycobacterial pulmonary disease. Published Oct. 2, 2023. Accessed Oct. 2, 2023.