How COVID-19 Changes the Lung Microbiome in People with Tuberculosis

Tuberculosis (TB) and COVID-19 both attack the lungs, and when they occur together clinicians face extra uncertainty about how best to treat patients. Manikandan Narayanan and colleagues set out to explore a less-studied part of that puzzle: the community of bacteria and other microbes living in the airway, as sampled from sputum. They collected sputum from four groups of people: those with TB only, those with COVID-19 only, people infected with both pathogens (labeled TBCOVID), and an uninfected control group. Rather than only measuring human immune responses, the team focused on the microbes present and how the communities differed between groups. To do this they used metagenomic analysis across all samples and also performed whole genome sequencing on a subset of TB-positive samples. The researchers applied careful bioinformatic quality checks to ensure the data were reliable before comparing microbial communities and searching for patterns linked to co-infection and treatment outcomes.

The study combined community-level sequencing with computational tools to identify which microbes and metabolic pathways were more or less common in each group. Bioinformatic analyses revealed clear differences between controls and the disease groups. Comparing the TBCOVID group to the TB-only group, the researchers found higher read counts of TB-causing bacteria in co-infected patients and shifts in specific bacterial species: Capnocytophaga gingivalis, Escherichia coli, Prevotella melaninogenica and Veillonella parvula varied in abundance between the groups. For functional insight they used PICRUSt2 to predict which microbial pathways were enriched; several pathways were significantly elevated in the TBCOVID group, including those related to pulmonary surfactant lipid metabolism such as the Cytidine diphosphate diacylglycerol (CDP-DAG) biosynthesis pathway, which showed a fold change of 7.46. Further clustering of these pathways identified a subgroup of individuals with adverse treatment outcomes; two people in that sub-cluster had respiratory pathogens like Stenotrophomonas maltophilia, information that could influence antibiotic choices.

These findings suggest that COVID-19 can reshape the airway microbial community in people with TB, not only by changing which species are present but also by altering the microbial metabolic activities that might affect lung biology. The presence of species such as Capnocytophaga gingivalis in co-infected patients but not in TB-only patients points to specific microbes that could help explain why co-infection sometimes leads to worse lung infection. Importantly, the study argues for routine profiling of co-microbial or co-pathogen communities: knowing the full microbial picture could allow clinicians to tailor antibiotic regimens to the actual pathogens present rather than using a one-size-fits-all approach. The authors note that these results should be validated in larger, independent and longitudinal studies to confirm whether adjusting treatments based on sputum microbial profiles truly improves TB outcomes in people with COVID-19 co-infection.