Clostridium, Bacteroides and Prevotella associates with increased fecal metabolites Trans-4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE)

Ruijie Meng; Wenya Dong; Jie Gao; Chunrong Lu; Chenchen Zhang; Qinghua Liao; Liang Chen; Huizhong Wu; Jiwen Hu; Wenjing Wei; Zhenyou Jiang

doi:10.1007/s12088-022-01003-2

Clostridium, Bacteroides and Prevotella associates with increased fecal metabolites Trans-4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE)

Indian J Microbiol. 2022 Sep;62(3):374-383. doi: 10.1007/s12088-022-01003-2. Epub 2022 Mar 24.

Authors

Ruijie Meng^#¹, Wenya Dong^#^{1

2}, Jie Gao¹, Chunrong Lu³, Chenchen Zhang⁴, Qinghua Liao⁴, Liang Chen⁴, Huizhong Wu⁴, Jiwen Hu⁵, Wenjing Wei⁴, Zhenyou Jiang¹

Affiliations

¹ Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China.
² Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, 511443 China.
³ Shenzhen Center for Chronic Disease Control, Shenzhen, 518102 China.
⁴ Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China.
⁵ Medical Laboratory of Shenzhen Luohu Hospital Group, Shenzhen, 518112 China.

^# Contributed equally.

Abstract

Purpose: To investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E).

Patients and methods: (1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without M. tuberculosis (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy.

Results: Mtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family Veillonellacea and Bateroidaceae and their genera Veillonella and Bacteroides significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut Clostridium, Bacteroides and Prevotella was closely related to the change of fecal metabolites such as Trans-4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy.

Conclusion: Anti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s12088-022-01003-2.

Keywords: 16S rRNA; Anti-TB chemotherapy; Fecal metabolome; Gut microbiome; Tuberculosis.