# The impact of the gut microbiome on rheumatoid arthritis treatment

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $177,498

## Abstract

PROJECT SUMMARY / ABSTRACT
 This 5-year K08 training program is designed to advance the career of Renuka Nayak, M.D., Ph.D.,
with the goal of preparing her for an independent research career as an academic physician-scientist. This
multidisciplinary proposal interrogates the role of the human gut microbiome in the treatment of rheumatoid
arthritis (RA) with methotrexate (MTX). At the conclusion of the award, Dr. Nayak will be an independent
investigator leading a multidisciplinary research lab that will make substantial contributions to the
understanding of the role of the gut microbiome in the personalized treatment of rheumatic diseases. Dr.
Nayak will gain this expertise through the combined guidance of: her primary mentor, Peter Turnbaugh, Ph.D.,
a leader in microbiome studies in nutrition and pharmacology; Katie Pollard, Ph.D., a world-renowned
statistician with expertise in large scale genomic and microbiome studies; Lindsey Criswell, M.D., an
international leader in genomic studies in patients with autoimmune disease; and Mary Nakamura, M.D., a
world-recognized leader in bone biology and bone immunology. Dr. Nayak and her mentors have developed a
formal training plan with didactics, seminars, workshops, and experimental research that will propel her
towards her career goals. The extensive resources at the University of California, San Francisco, an entirely
biomedical campus with world experts and physician-scientists, as well as the deep commitment and support
of her Department and Division will facilitate Dr. Nayak's pathway to independence and her long-term goals to
advance the care of rheumatology patients through personalized medicine.
 RA is an inflammatory arthritis resulting in irreversible damage unless effective therapy is provided
quickly. Oral MTX is first-line therapy for RA, but is ineffective in 50-70% of patients; clinicians currently employ
a “trial and error” approach to treatment. While many have studied whether genetics or environmental factors
predict response, none have examined the role of the gut microbiome. Dr. Nayak's research has demonstrated
that human gut bacteria metabolize MTX, and that fecal microbiomes from healthy individuals vary in their
ability to metabolize MTX. Additionally, work from her collaborators suggests that the baseline, pre-treatment
microbiome is associated with MTX response in RA patients. These observations motivate Dr. Nayak to test
the hypothesis that gut bacterial metabolism of MTX interferes with RA treatment. She will investigate the
following independent and complementary aims: (1) define a mechanism for the role of the baseline
microbiome in clinical MTX response, (2) elucidate the effects of MTX treatment on bacterial drug metabolism,
and (3) establish an in vivo model to test the relevance of MTX metabolism by the microbiome. The proposed
studies will provide insight into the mechanisms by which the microbiome affects the treatment of
rheumatologic disease. Defining these mechani...

## Key facts

- **NIH application ID:** 10229456
- **Project number:** 5K08AR073930-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Renuka Rajendra Nayak
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $177,498
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229456

## Citation

> US National Institutes of Health, RePORTER application 10229456, The impact of the gut microbiome on rheumatoid arthritis treatment (5K08AR073930-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229456. Licensed CC0.

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