Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

Objective: To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB).

Methods: In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods.

Results: Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as , compared with control treatment. However, the relative abundance of , , and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment.

Conclusion: Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.