# The role of bacteria-produced indole in the development of autoimmune arthritis

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $330,976

## Abstract

ABSTRACT
Emerging data suggest that host-microbe interactions, which modulate host immunity, may play an important
role in the development of rheumatoid arthritis (RA). Using the well-characterized collagen-induced arthritis
(CIA) model, we have published our findings that depletion of the microbiota through administration of broad-
spectrum antibiotics during the phase of disease when autoantibodies are developing but observable arthritis is
not present results in >95% reduction in disease severity. Preliminary data generated by our group identified
the bacteria-produced metabolite indole, derived from dietary tryptophan, correlated with the development of
CIA. Oral administration of indole to antibiotic-treated mice induced for CIA resulted in increased disease
severity. Therefore, we hypothesize that the expansion of indole-producing bacteria exacerbate CIA through
the development of mucosal germinal centers in which indole stimulates antibody glycosylation through aryl
hydrocarbon receptor signaling. To understand how the microbe-derived indole modulates CIA, in Aim 1, we
will first identify the bacterial source(s) of indoles during the course of CIA by using selective colonization of
germ free mice. In Aim 2, we will evaluate the mechanism by which indole affects collagen-specific Tfh and B
cell differentiation during the course of CIA. Aim 3 will then focus on how indole affects collagen autoantibody
pathogenicity through the stimulation of B cell glycosylation enzymes. Completion of these studies will provide
a novel insight into how intestinal bacteria modulate the development of autoimmune arthritis and inform future
translational studies in humans with RA.

## Key facts

- **NIH application ID:** 10132989
- **Project number:** 5R01AR075033-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kristine A. Kuhn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,976
- **Award type:** 5
- **Project period:** 2019-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132989

## Citation

> US National Institutes of Health, RePORTER application 10132989, The role of bacteria-produced indole in the development of autoimmune arthritis (5R01AR075033-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132989. Licensed CC0.

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