Dissecting the effect of single- and co-infection of TB and COVID-19 pathogens on the sputum microbiomeOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat Was Studied?
This observational cross-sectional study characterized the sputum microbiome across single infection and co-infection with the pathogens of tuberculosis (TB) and COVID-19. Investigators compared four groups: TB only, COVID-19 only, TB and COVID-19 co-infection (TBCOVID), and uninfected controls. The airway bacterial community was profiled by 16S rRNA (V3-V4) amplicon sequencing with metagenomic analysis, complemented by whole-genome sequencing of Mycobacterium tuberculosis in a subset to assess strain-level differences and by functional pathway inference.
Who Was Studied?
Participants were recruited in Chennai, India, through IIT Madras and the ICMR National Institute for Research in Tuberculosis, with 1,132 sputum samples initially screened and a stratified subset of 82 samples analyzed (24 TB, 10 COVID-19, 24 TBCOVID, and 24 controls). TB and TBCOVID cases were newly diagnosed, none were HIV co-infected, and the cohort was predominantly male (about 85%), with roughly 30% tobacco users and 48% alcohol consumers. Previously treated TB patients and those with unknown HIV status or inconsistent treatment regimens were excluded.
What Were the Key Findings?
Alpha diversity (richness, Shannon, Simpson) did not differ significantly among groups, but beta diversity by PERMANOVA distinguished TBCOVID from both TB (P=0.006) and controls (P=0.02), while COVID-only versus control did not separate (P=0.665). Relative to TB alone, the TBCOVID community was enriched for Capnocytophaga gingivalis, Prevotella melaninogenica, Veillonella parvula, and Escherichia coli and depleted of Rothia mucilaginosa and Saccharibacteria (TM7), and 30 functional pathways were upregulated, notably pulmonary surfactant lipid metabolism (fold change 7.46) and CDP-diacylglycerol biosynthesis, with several pathways attributable to Stenotrophomonas maltophilia. Clustering by these pathways largely separated TB from TBCOVID samples, and the co-infection-associated cluster carried roughly twice as many recognized respiratory pathogens and more adverse outcomes.
What Are the Implications?
The findings suggest that COVID-19 co-infection is associated with a distinct sputum microbiome and metabolic profile in TB patients, including enrichment of opportunistic respiratory organisms such as S. maltophilia that has been linked to multidrug-resistant TB, raising the possibility that dysbiosis accompanies more complicated disease courses. Because the analysis is cross-sectional with modest group sizes and no diagnostic classifier or AUC was derived, the authors emphasize that the associations are exploratory and do not establish causation or prediction. Strain-level whole-genome sequencing showed no clear M. tuberculosis genetic differences between TB and TBCOVID groups, pointing to host-microbiome rather than pathogen-genotype drivers, though residual confounding from treatment and antibiotic exposure cannot be excluded.