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

Chunli Wu; Hengzhong Yi; Yanmei Hu; Danlin Luo; Zhigang Tang; Xinmin Wen; Yong Zhang; Mi Tang; Lizhi Zhang; Shu Wu; Mengshi Chen

doi:10.3389/fcimb.2023.1127916

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

Front Cell Infect Microbiol. 2023 Apr 28:13:1127916. doi: 10.3389/fcimb.2023.1127916. eCollection 2023.

Authors

Chunli Wu¹, Hengzhong Yi², Yanmei Hu², Danlin Luo², Zhigang Tang², Xinmin Wen², Yong Zhang², Mi Tang², Lizhi Zhang³, Shu Wu², Mengshi Chen¹

Affiliations

¹ Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
² 6th Medical Department, Hunan Province Chest Hospital, Changsha, Hunan, China.
³ Orthopedics and integration Medical Department, Hunan Province Chest Hospital, Changsha, Hunan, China.

Abstract

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 Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, 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 Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Keywords: differential function; differential species; intestinal microbiota; rifampicin-resistant tuberculosis; second-line anti-tuberculosis drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use
Cross-Sectional Studies
Gastrointestinal Microbiome*
Humans
Mycobacterium tuberculosis*
Rifampin / pharmacology
Rifampin / therapeutic use
Tryptophan
Tuberculosis* / drug therapy
Tuberculosis, Multidrug-Resistant* / drug therapy

Substances

Antitubercular Agents
Rifampin
Tryptophan

Grants and funding

This study was supported by Natural Science Foundation of Hunan Province (2019JJ80044); Science and Technology Innovation Platform and Talent Program of Hunan Province (2018SK7003). The funding organization played no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.