Exploring the Relationship between Tuberculosis and Gut Microbiota: A Multi-Omics Approach

Abstract

Background A number of unanswered questions remain regarding the relationship between tuberculosis (TB) and our gut microbiota, which consists of microbial life within our bodies. Multi-omics is an effective strategy to reveal the mechanism of disease, including tuberculosis, but there are few reports on TB by using multi-omics. 

Methods: In this study, we integrated omics analysis to investigate the altered gut microbiota and fecal metabolomic profiles in TB patients using 16S rDNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). A total of 29 untreated TB patients and 29 health controls (HCs) were recruited in this study. we sequenced the 16S rDNA V3-V4 variable regions to obtain the intestinal microbiota and evaluated the diagnostic ability for TB of the differential intestinal microbiota. Then the fecal metabolic profiles were investigated by LC-MS. 

Results: the intestinal microbiota in TB patients was significantly changed compared with that in HCs. Nine differential intestinal microbiota (genus),including Akkermansia, Erysipelotrichaceae, Clostridium_innocuum_group, Eubacterium_hallii_group, Eubacterium_ventriosum_group, Lachnospira, Ruminococcus_2, Roseburia and Blautia, can distinct TB patients from HCs with high accuracy (sensitivity 79.3%, specificity 89.7%). A total of 33 significantly differential-metabolites in TB patients were identified by the metabolomics analysis, and the indole-3-propionic acid (IPA) enriched in TB patients showed the strongest correlation with intestinal microbiota. 

Conclusions: The gut microbiota composition and metabolic profiles significant changed in TB patients in TB patients, which can be used as potential preventive and therapeutic targets for TB, and IPA enriched in TB patients may play an important role in the pathogenesis of TB.

Note:
Funding declaration: This work was funded by the National Natural Science Foundation of China [82272416]; Sichuan Natural Science Foundation [2022NSFSC0747]; National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX10715003-001]; and 1.3.5 project for disciplines of excellence-Clinical Search Incubation Project, West China Hospital, Sichuan University [2020HXFH015].

Conflict of Interests: The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval: Approval was granted by the Ethics Committee of West China Hospital of Sichuan University [No.2019(829)]. Informed consent was obtained from all individual participants included in the study.

Keywords: Tuberculosis, gut microbiota, Metabolomics, Indole-3-Propionic acid