# Metabolic and Immune Consequences of Antibiotic-Related Microbiome Alterations during TB Treatment

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $188,082

## Abstract

ABSTRACT
 Tuberculosis (TB) remains a public health problem worldwide, but yet effective vaccine and short
treatment regimens are missing due in part to the lack of a complete understanding of the host immune
response and its dynamic during treatment. TB patients are at 13 times higher risk of developing another
episode of TB than the general population. Previous studies have shown that the major TB drugs, isoniazid,
rifampin, ethambutol and pyrazinamide, create a profound long-standing alteration of gut microbiota that may
play a negative role on host immune response. This may thereby impact treatment efficacy and duration, and
furthermore expose patients to future TB infections. In fact, this resulting dysbiosis from TB treatment
correlates well with the magnitude of TB bacterial clearance during therapy, which decreases significantly as
the treatment progresses. However, at present it is not known what are the consequences of the dysbiosis
resulting from a treatment taken by many millions of patients worldwide. This project will investigate the direct
link between mucosal microbial profiles and the microbial metabolic byproducts such as short chain fatty acids
(SCFAs) and retinoic acid (RA), that could ultimately impact the microbiome-liked immune pathways including
regulatory T cells, autophagy, IL-10, IL-17, IL-22 and TGF-beta. In addition to bacteria, this project will
determine changes and impacts from parasites, fungi and viruses’ compositions, which were missed in
previous TB studies. This study will address how drug related-dysbiosis would impact microbiome-derived
metabolites that are important for immune cells responsiveness to TB. Understanding the dynamic of
microbiome related-immune disorders during and after treatment will elucidate the contribution of microbiome
in TB immune response in general with applications in designing future better vaccines and more effective
treatments. The specific aims of the project are to: 1) Determine the longitudinal dynamics of the microbiome
immune metabolic functions during and after tuberculosis therapy, and 2) Determine the evolution of
microbiome linked inflammatory markers during and after tuberculosis therapy. This project may lead to new
TB vaccine and treatment strategies.

## Key facts

- **NIH application ID:** 9941043
- **Project number:** 5R21AI148033-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** MAMOUDOU MAIGA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,082
- **Award type:** 5
- **Project period:** 2019-06-03 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941043

## Citation

> US National Institutes of Health, RePORTER application 9941043, Metabolic and Immune Consequences of Antibiotic-Related Microbiome Alterations during TB Treatment (5R21AI148033-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9941043. Licensed CC0.

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