# The impact of the gut microbiome on rheumatoid arthritis treatment

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $93,860

## Abstract

PROJECT ABSTRACT
 Rheumatoid arthritis (RA) is an inflammatory arthritis resulting in irreversible damage unless effective
therapy is provided quickly. Oral methotrexate (MTX) is first-line therapy for RA but is inadequate in 50-70% of
patients; clinicians currently employ a “trial and error” approach to treatment. While many have studied whether
human genetics or environmental factors predict MTX response, none have examined the role of the gut
microbiome. We recently showed that the gut microbiome of RA patients predicts MTX responsiveness. We
further showed that RA patients harboring gut microbiota that quickly metabolized MTX were less likely to
respond to MTX, suggesting gut microbial metabolism of MTX contributes to response. The genes responsible
for metabolism and the causal impact of microbial metabolism on MTX pharmacology remains unknown. This
knowledge could transform our understanding of modifiable factors that affect MTX response; they could provide
a foundation for the design of therapies that modify or target the gut microbiota. Thus, we seek to test the
hypothesis that gut bacterial metabolism of MTX interferes with RA treatment. Dr. Nayak and a trainee, supported
by this administrative supplement, will investigate the following independent and complementary aims: (1)
identify gut microbial genes responsible for MTX metabolism, (2) quantify the impact of the gut microbiome on
MTX metabolism in vivo. The proposed studies will provide insight into the mechanisms by which the microbiome
affects the treatment of rheumatologic disease. Defining these mechanisms will advance our knowledge of the
role of the microbiome in precision medicine.

## Key facts

- **NIH application ID:** 10605661
- **Project number:** 3K08AR073930-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Renuka Rajendra Nayak
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $93,860
- **Award type:** 3
- **Project period:** 2018-08-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10605661

## Citation

> US National Institutes of Health, RePORTER application 10605661, The impact of the gut microbiome on rheumatoid arthritis treatment (3K08AR073930-05S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10605661. Licensed CC0.

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