# Can circulating bile acids predict knee OA progression?

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $168,839

## Abstract

Can Circulating Bile Acids Predict Knee OA Progression?
Osteoarthritis (OA) is the most common form of arthritis. Biomarkers that could predict the individuals with similar
risk factors that would progress is an unmet need. Increasing evidence indicates that OA progression is mediated
by low-grade systemic (obesity) and local (inflamed synovium) inflammation. Recently, a positive correlation
between serum lipopolysaccharide (LPS), a key proinflammatory product of the microbiome, obesity, joint
inflammation, and OA severity was reported and suggests an influence of microbiome and gut permeability in
the pathogenesis of OA. However, the extent to which low-grade inflammation-based mediators can predict OA
progression remains unclear.
Once known only for their role in nutrients absorption, primary bile acids (BAs) such as chenodeoxycholic and
cholic acid, and secondary BAs, such as deoxycholic and lithocholic acid, are signaling molecules generated
from cholesterol breakdown by the interaction of the host and intestinal microbiota that modulate intestinal
permeability. These bioactive metabolites act on several receptors that are highly expressed in cells of innate
immunity. They regulate diverse metabolic and inflammatory pathways in multiple cell types and tissues.
Importantly, human obesity is associated with altered BA metabolism and increased intestinal permeability.
Our preliminary studies in knee OA (KOA) subjects show that circulating BAs are significantly associated with
radiographic KOA and outcome scores. The most significant association was for cholic acid, that was significantly
associated with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (r=0.44, p=0.01).
Interestingly, BAs also associated with synovitis (glycoursodeoxycholic acid, r=0.39, p=0.04), and with LPS
binding protein (LBP), a biomarker of KOA progression (cholic acid, r=0.41, p=0.03). Of interest, these
associations differed between obese and non-obese subjects. These observations suggest distinct BAs may be
key mediators of OA development and progression.
Therefore, we hypothesize that (1) BA profiles will be associated with MRI phenotypes of KOA, especially with
synovitis/effusion; 2) altered BA profiles are associated with KOA progression. To address this goal, we will
conduct our investigation in the carefully phenotyped FNIH/OAI Biomarkers Project cohort, with
semiquantitative and quantitative MRI scores and clinical and radiographic outcomes at 48 months available in
the OAI website, to relate circulating BAs with synovitis and KOA progression. The proposed experiments are
high risk and we will determine if 1) specific circulating BA are related to synovitis and KOA 2) define elements
of lipid pathogenesis that link KOA outcomes among all persons at risk. However, these studies might provide a
foundation to determine phenotypes of KOA and investigations into novel personalized interventions to reduce
KOA-related morbidity.

## Key facts

- **NIH application ID:** 10811585
- **Project number:** 5R21AR082029-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Monica Guma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $168,839
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811585

## Citation

> US National Institutes of Health, RePORTER application 10811585, Can circulating bile acids predict knee OA progression? (5R21AR082029-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10811585. Licensed CC0.

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