Treatment-naive patients with active pulmonary tuberculosis exhibited reduced gut microbial diversity, enrichment of pro-inflammatory genera Streptococcus and R. gnavus, and upregulation of purine and pyrimidine metabolic pathways compared to healthy controls.
Key Findings
Results
ATB patients showed significantly lower gut microbial α-diversity than healthy controls.
33 treatment-naive patients with newly diagnosed active pulmonary tuberculosis (ATB) were compared to 30 healthy controls (HC)
All α-diversity metrics showed statistically significant differences (all P < 0.05)
Fresh morning fecal samples were analyzed using 16S rRNA gene high-throughput sequencing
Samples were collected from treatment-naive, newly diagnosed patients to avoid confounding by antibiotic treatment
Results
Gut microbial community structure was significantly different between ATB patients and healthy controls.
Principal coordinate analysis (PCoA) based on Bray-Curtis distances was used to assess β-diversity
Permutational multivariate analysis of variance (PERMANOVA) confirmed significant overall dissimilarity (R2 = 0.31, p = 0.005)
The R2 value of 0.31 indicates that ATB/HC group membership explained approximately 31% of variance in microbial community composition
Results
At the phylum level, Firmicutes and Bacteroidetes were more abundant while Proteobacteria was less abundant in ATB patients relative to healthy controls.
Phylum-level compositional differences were identified through 16S rRNA sequencing
Firmicutes and Bacteroidetes showed higher relative abundances in the ATB group
Proteobacteria was less abundant in ATB patients compared to healthy controls
These phylum-level shifts suggest broad restructuring of the gut microbial community in active tuberculosis
Results
Streptococcus, R. gnavus, and Parabacteroides were significantly enriched in ATB patients at the genus level, while Bifidobacterium, Pseudomonas, Megamonas, and Faecalibacterium were depleted.
Genus-level differences were identified through taxonomic profiling of 16S rRNA sequencing data
LEfSe analysis confirmed pro-inflammatory genera Streptococcus and R. gnavus as markedly enriched group-specific signature taxa in the ATB group
Faecalibacterium, a genus commonly associated with anti-inflammatory effects, was among the depleted taxa in ATB patients
Bifidobacterium depletion in ATB patients may reflect reduced beneficial microbiota
Results
ROC analysis identified Streptococcus and R. gnavus as candidate discriminative biomarkers for active tuberculosis within this cohort.
ROC curve analysis was conducted to evaluate the internal discriminative ability of candidate differential genera
Streptococcus yielded an area under the curve (AUC) of 0.836
R. gnavus yielded an AUC of 0.805
The authors note this reflects internal discriminative ability within a single small cohort, not validated external predictive performance
Results
Predictive functional profiling revealed significant upregulation of purine and pyrimidine nucleotide metabolism pathways in ATB patients.
Functional predictions were generated using KEGG pathway analysis applied to 16S rRNA sequencing data
Purine and pyrimidine nucleotide metabolism pathways were significantly upregulated in the ATB group compared to healthy controls
Obvious intergroup differences in microbial metabolism were demonstrated
These metabolic pathway shifts are associated with active MTB infection according to the authors
What This Means
This research suggests that people newly diagnosed with active pulmonary tuberculosis (TB) have notable differences in their gut bacteria compared to healthy individuals, even before starting any treatment. Using genetic sequencing of stool samples from 33 TB patients and 30 healthy controls, the researchers found that TB patients had less diversity in their gut microbiome overall, and a distinctly different community of bacteria. Specifically, bacteria associated with inflammation — particularly Streptococcus and a species called Ruminococcus gnavus — were more common in TB patients, while beneficial bacteria like Bifidobacterium and Faecalibacterium were less common.
The study also used statistical modeling to test whether these specific bacterial genera could help distinguish TB patients from healthy people. Streptococcus and R. gnavus both showed reasonable discriminative ability within this dataset (AUC values of 0.836 and 0.805, respectively), though the authors caution this was an internal analysis in a small cohort and does not represent validated external performance. Additionally, computer-predicted analysis of bacterial gene functions suggested that the metabolic pathways related to purine and pyrimidine (components of DNA and RNA) were more active in the gut bacteria of TB patients.
This research suggests there may be a meaningful connection between tuberculosis infection and gut microbiome disruption, possibly involving inflammation and altered cellular metabolism. While this was a small, single-center study using predictive rather than direct metabolic measurements, the findings point toward potential gut microbiome-based biomarkers for TB and raise questions about whether the gut microbiome plays a role in TB disease or its progression. Larger, externally validated studies would be needed to confirm whether these microbial signatures could be clinically useful.
Chen Z, Liu G, Wang Y, Zhong J, Mo Y, Liang D, et al.. (2026). Research on Gut Microbiota Features and Potential Biomarkers in Patients with Pulmonary Tuberculosis.. Pathogens (Basel, Switzerland). https://doi.org/10.3390/pathogens15080805