Intestinal microbiota and tuberculosis: Insights from Mendelian randomization

Area of Science:

• Microbiome research
• Infectious disease epidemiology
• Genetic epidemiology

Background:

• Respiratory tuberculosis (RTB) is a major global health issue.
• Observational studies suggest a link between gut microbiota and RTB, but causality is unproven.
• Understanding this relationship is crucial for developing new prevention and treatment strategies.

Purpose of the Study:

• To investigate the potential causal relationship between gut microbiota composition and respiratory tuberculosis (RTB).
• To identify specific gut microbial taxa causally associated with RTB using genetic data.
• To leverage Mendelian randomization (MR) for robust causal inference.

Main Methods:

• Utilized Mendelian randomization (MR) analysis.
• Employed genome-wide association study (GWAS) data for gut microbiota from the MiBioGen Consortium (N=115,893).
• Used two Finnish Genetic Consortium datasets (Fingen R9 TBC RESP and Fingen R9 AB1 RESP) for RTB cases.

Main Results:

• The inverse variance weighting (IVW) method identified significant associations.
• Seven microbial taxa were significantly associated with RTB in the TBC RESP dataset.
• Four microbial taxa were linked to RTB in the AB1 RESP dataset, with Lachnospiraceae UCG010 consistently identified in both.
• Lachnospiraceae UCG010 showed a significant causal association with RTB in both datasets (OR=1.799, 95% CI=1.243-2.604 in TBC RESP; OR=2.131, 95% CI=1.088-4.172 in AB1 RESP).

Conclusions:

• This study provides genetic evidence for a causal relationship between specific gut microbiota and respiratory tuberculosis.
• Findings suggest that gut microbiota composition plays a role in RTB pathogenesis.
• Identifies potential microbial targets for future therapeutic interventions against RTB.