Gut Microbiota in Patients with Tuberculosis Associated with Different Drug Exposures of Antituberculosis Drugs.

Interindividual variability in drug exposure can significantly influence treatment outcomes and may lead to drug concentration-related side effects during tuberculosis (TB) treatment. Although the gut microbiota is known to affect drug metabolism, its impact on anti-TB drugs has not been thoroughly explored. This study sought to elucidate the relationship between pre-treatment gut microbiota and drug exposure levels among patients with pulmonary TB. Two cohorts were analyzed: a discovery cohort (N = 99) and a validation cohort (N = 32), both comprising patients undergoing anti-TB therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. The gut microbiota patterns of participants from the discovery cohort and the validation cohort were profiled by 16S rRNA gene sequencing and metagenomics, respectively. Analyses of both cohorts robustly established a positive association between pre-treatment microbial diversity and drug exposure, as well as significant differences in gut microbiota composition across various drug exposure groups. At the species level, Faecalibacterium prausnitzii was positively associated with drug exposure to rifampicin. Moreover, functional analysis revealed that starch and sucrose metabolism and secondary bile acid biosynthesis were more abundant in the high drug exposure group. To identify biomarkers capable of stratifying patients based on their drug exposure levels, 11 taxa, represented by Faecalibacterium, were selected in the discovery cohort (AUC = 0.992) and were confirmed in the validation cohort with high predictive accuracy (AUC = 0.894). This study demonstrated a correlation between microbial dysbiosis and reduced exposure to anti-TB medications. Optimizing treatment by regulating gut microbiota to improve drug exposure levels requires further validation through larger scale multicenter clinical trials.