Cross-sectional associations of radiographic multiple joint osteoarthritis and symptoms, laboratory values and the gut microbiota: A multimodal study in humans and pet dogs

Amanda E Nelson; Liubov Arbeeva; Kelly Johnson; Serena Savage-Guin; Tessa Walker; Masataka Enomoto; Christina Stevens; Milja Koskinen; Tracey Cole; Savannah Aker; Connor Thonen-Fleck; M Andrea Azcarate-Peril; Richard F Loeser; Jordan B Renner; Yvonne M Golightly; B Duncan X Lascelles

doi:10.1016/j.ocarto.2025.100682

Cross-sectional associations of radiographic multiple joint osteoarthritis and symptoms, laboratory values and the gut microbiota: A multimodal study in humans and pet dogs

Osteoarthr Cartil Open. 2025 Sep 23;7(4):100682. doi: 10.1016/j.ocarto.2025.100682. eCollection 2025 Dec.

Authors

Amanda E Nelson^{1

2}, Liubov Arbeeva¹, Kelly Johnson¹, Serena Savage-Guin¹, Tessa Walker¹, Masataka Enomoto³, Christina Stevens³, Milja Koskinen³, Tracey Cole³, Savannah Aker³, Connor Thonen-Fleck³, M Andrea Azcarate-Peril⁴, Richard F Loeser^{1

2}, Jordan B Renner¹, Yvonne M Golightly^{1

5}, B Duncan X Lascelles^{1

3}

Affiliations

¹ Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Translational Research in Pain and Comparative Pain Research and Education Center, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
⁴ Center for Gastrointestinal Biology and Disease (CGIBD), Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, UNC Microbiome Core, University of North Carolina, Chapel Hill, NC, USA.
⁵ College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, USA.

Abstract

Objective: To describe the frequency of multiple joint osteoarthritis (MJOA) and symptoms, and associations with fecal microbial diversity and composition, in cohorts of humans and dogs.

Design: Human participants enrolled in the community-based Johnston County Health Study (JoCoHS), and an independent cohort of pet dogs, were included. Questionnaires, functional assessments, standardized multiple joint radiographs, and pain assessments, blood and fecal samples were obtained. Microbiome analysis was done by 16S rRNA amplicon sequencing. MJOA was defined as ≥3 unique joint sites involved; symptom burden was based on self-reported/proxy measures of pain. Descriptive statistics and Spearman correlations with Benjamini-Hochberg correction were used to determine relationships among lab tests, pain, and microbiome diversity measures.

Results: Human participants (n = 100, 63 % women, mean age 56 years, mean body mass index 34 kg/m²) and 115 pet dogs (40 % spayed females, 57 % neutered males, mean age 8 years, mean weight 27 kg) were included; 20 % had radiographic MJOA (rMJOA). Microbial α-diversity did not differ between participants with or without rMJOA. However, lower levels of the Christensenellaceae R-7 group and Lachnoclostridium in humans, and the butyrate-producing bacterium, Faecalibacterium in dogs, were moderately correlated with greater pain severity, as were higher levels of Escherichia-Shigella in dogs. Faecalibacterium was more abundant in humans without rMJOA.

Conclusions: These two cohorts demonstrated remarkably similar frequencies of rMJOA (∼20 %), supporting the use of dogs to model naturally occurring MJOA. Taxa potentially related to rMJOA and pain were identified in this preliminary analysis, providing new insights into links between dysbiosis and MJOA.

Keywords: Chronic disease; Cohort studies; Companion animals; Microbiome; Osteoarthritis.

Abstract

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