# Effects of TB and TB treatment on the pediatric intestinal microbiome

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $243,250

## Abstract

PROJECT SUMMARY/ABSTRACT
While nearly one quarter of the world’s population is latently infected with Mycobacterium tuberculosis, only a
small fraction develops active TB. In 2017, 10 million people developed TB, including 1 million children. Risk
factors for progression to active TB after aerosolized exposure are, in large part, related to age and immunologic
competency. However, improved methods are needed to identify people at highest risk of developing active TB.
 There is a growing appreciation that the microbiome—comprised of the trillions of organisms that live
within the human—plays essential roles in the regulation of host metabolism and immunity. Immune pathways
include the ability of commensal organisms to outcompete invasive pathogens and the ability of certain flora to
stimulate innate immune responses, subsequently influencing adaptive responses that promote mucosal
immunity. While the majority of the microbiome is found in the human intestines, additional important flora reside
within various other compartments, most relevant of which includes the lungs; there is an emerging appreciation
for the cross-talk between these two compartments, termed the gut-lung axis. Regarding TB, little is understood
about ways in which the microbiome may impact risk of progression to active TB or disease outcomes. Although
it is well known that the use of antimicrobials leads to a disruption in the intestinal flora, the impacts of first-line
TB treatment with rifampin, isoniazid, pyrazinamide and ethambutol on the microbiome are understudied. The
recommended course of TB treatment is lengthy—at least six months; therefore, there is a concern that this
period of continuous antimicrobial exposure can have long-term effects on the microbiome.
 In this application, we propose to evaluate the intestinal microbiota from pediatric participants who were
recruited in a cohort study of children from rural Tanzania undergoing evaluation for TB disease; we will use
stool samples collected at three time points over six months, including a timepoint prior to any TB treatment
initiation. We hypothesize that prior to TB treatment initiation, “cases” with TB will demonstrate perturbations in
the intestinal microbiome that are distinguishable from “control” children without TB. Additionally, serial
assessments of the intestinal microbiome will demonstrate how TB treatment is associated with alterations in
microbiologic membership and functional potential compared to “control” children who did not need or receive
TB treatment. We will test our hypotheses via the following aims: 1) evaluate the intestinal microbiome among
children with TB disease compared children who have been ruled out from having TB disease, and 2) determine
the longitudinal impacts of TB treatment on the composition, diversity, and resilience of the intestinal microbiome
among children on TB treatment compared to controls. DNA extraction from stool samples and metagenomic
sequencing will be conducte...

## Key facts

- **NIH application ID:** 10196992
- **Project number:** 5R21AI154259-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Tania A Thomas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,250
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196992

## Citation

> US National Institutes of Health, RePORTER application 10196992, Effects of TB and TB treatment on the pediatric intestinal microbiome (5R21AI154259-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196992. Licensed CC0.

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