Fecal and Sputum Microbiota and Treatment Response in Patients with Mycobacterium abscessus Pulmonary Disease

Background: The microbiota is a potential source of biomarkers for clinical outcomes in chronic respiratory conditions, but its role in Mycobacterium abscessus pulmonary disease (PD) remains unexplored. We aimed to identify microbial signatures in fecal and sputum microbiotas associated with treatment response in patients with M. abscessus PD.

Methods: We conducted a cohort study prospectively enrolling patients undergoing antibiotic treatment for M. abscessus PD. Fecal and sputum samples were collected before, and 2 weeks and 6 months after, treatment initiation. 16S rRNA amplicon sequencing approach was used to characterize the microbiotas. After categorizing patients as early treatment responders and non-responders based on sputum culture results at 2 weeks, we elucidated the differences in their diversity and composition of microbiotas.

Results: Among 32 patients enrolled, 27 patients (median 66 years, 85.2% women, 48.1% with subspecies abscessus) were included for microbiota analysis. Fifteen patients (55.6%) achieved negative conversion at 2 weeks, which was maintained in 14 (93.3%) after 6 months. Alpha-diversity of the fecal microbiota after 2 weeks of treatment decreased significantly in responders, but not in non-responders (P=0.029). Increased abundance of Eubacterium hallii group in baseline fecal microbiota was indicative of unresponsiveness to antibiotics, whereas an increase in Enterococcus in fecal microbiota at week 2 was linked with favorable response. Increased abundance of Burkholderia-Caballeronia-Paraburkholderia and Porphyromonas in baseline, and decreased abundance of Rothia in week 2 sputum microbiota were also associated with good treatment response.

Conclusions: In M. abscessus PD, changes in microbial diversity and compositional signatures vary with treatment response.