# Gut Microbiome and Pharmacokinetic Variability in Tuberculosis and Diabetes

> **NIH NIH K23** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $202,217

## Abstract

PROJECT SUMMARY/ABSTRACT
There are significant knowledge gaps in understanding the mechanisms and biological predictors of low drug
exposures and treatment failure in patients with tuberculosis (TB) and type 2 diabetes mellitus (DM). To address
the impact of DM on poor TB outcomes, we propose an interdisciplinary mentored research and training plan to
investigate gut microbiome-mediated variation of anti-TB drug pharmacokinetics (PK) in DM and non-DM TB
patients in an ongoing prospective, observational PK trial investigating isoniazid, rifampin, and pyrazinamide in
TB patients. Specific Aim 1 will quantify the effect of DM and gut microbiota alpha diversity on the
bioavailability of oral anti-TB drugs in patients treated for active TB, by linking pharmacometric modeling
with DM and measures of the gut dysbiosis in active TB patients with and without DM. Specific Aim 2 will
characterize the relationship of gut microbiota alpha diversity and diabetes in patients with active TB,
by conducting a comprehensive prospective analysis of the human gut microbiome from clinical stool specimens.
Upon successful completion of the proposed K23 research, we expect our contribution to 1) establish the
previously undescribed impact of the human gut microbiome as a significant covariate to explain the
heterogeneity of drug PK in patients receiving active TB treatment and, 2) demonstrate the distinctive relationship
between DM and gut microbiome diversity and composition among patients with TB. These contributions will be
significant because they are expected to provide strong scientific justification for a novel mechanism for the
previously unexplained variability of anti-TB drug PK and TB treatment response among patients with TB/DM.
The proposed research is innovative because it aims to identify the gut microbiome as a novel mechanism
underlying the heterogeneity of anti-TB drug PK. The overall goal of this K23 proposal is to train Navaneeth
Narayanan, PharmD, MPH for a career as an independent investigator in pharmacomicrobiomics, the study of
the effect of microbiome variation on therapeutic response by regulating drug PK and pharmacodynamics (PD),
with a specific career emphasis on the treatment and outcomes of TB and other infectious diseases. The career
development plan includes training in human microbiome research, under the mentorship of Dr. Martin Blaser,
and pharmacometrics, an interdisciplinary science of quantitative clinical pharmacology and systems biology that
involves expertise in mathematical modeling to characterize and predict drug PK and PD. Dr. Narayanan will
also be mentored by Dr. Scott Heysell, an international expert in anti-TB pharmacology and TB clinical research.
The proposed K23 project will provide an integrated plan of mentored patient-oriented research, career
development activities, and formal training in microbiome research and pharmacometrics. Guided by expert
mentors and collaborators, the research and training activities outl...

## Key facts

- **NIH application ID:** 10893634
- **Project number:** 5K23AI159396-04
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Navaneeth Narayanan
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $202,217
- **Award type:** 5
- **Project period:** 2022-07-08 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893634

## Citation

> US National Institutes of Health, RePORTER application 10893634, Gut Microbiome and Pharmacokinetic Variability in Tuberculosis and Diabetes (5K23AI159396-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893634. Licensed CC0.

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