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Annals of translational medicine2024; 12(6); 112; doi: 10.21037/atm-24-109

Correlation of fecal microbiome dysregulation to synovial transcriptome in an equine model of obesity associated osteoarthritis.

Abstract: Osteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immune transcriptome in OA pathophysiology. Unassigned: Feces, peripheral blood mononuclear cells (PBMCs), and SF cells were isolated from healthy skeletally mature horses (n=12; 6 males, 6 females) and those with OA (n=6, 2 females, 4 males). Horses were determined to have OA via lameness evaluation, response to intra-articular (IA) diagnostic analgesia, and radiographic and arthroscopic evidence. Horses were excluded who had received medications or joint injections within 2 months. Cytokine analyses of plasma and SF were performed via multiplex immunoassay. Fecal bacterial microbial 16s DNA sequencing was performed and correlated to bulk RNA sequencing of SF cells and PBMC performed using an Illumina based platform. Unassigned: Horses with OA had higher body condition scores (P=0.009). Cytokines were elevated in plasma [interleukin (IL)-2, IL-6, IL-18, interferon gamma (IFN-γ), interferon gamma inducible protein 10 (CXCL10 or IP-10), granulocyte colony-stimulating factor (G-CSF)] and SF (IL-1β, IL-6, IL-17A, IL-18, IP-10, G-CSF) in OA. Microbial principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity for β-diversity demonstrated distinct grouping of samples from OA versus healthy horses (P=0.003). Faith alpha diversity was reduced in OA (P=0.02). Analysis of microbiome composition showed differential relative abundance of taxa on multiple levels in OA. Specific phyla (Firmicutes, Verrucomicrobia, Tenericutes, Fibrobacteres), correlated to transcriptomic differences related to cell structure, extracellular matrix, collagen, laminin, migration, and motility, or immune response to inflammation in OA. Unassigned: These findings provide compelling evidence for a link between obesity, gut microbiome dysbiosis and differential gene expression in distant joint sites associated with development of OA in a relevant large animal model, establishing a connection here that provides a platform from which development of therapeutic interventions targeting the gut microbiome can build.
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Publication Date: 2024-12-13 PubMed ID: 39817240PubMed Central: PMC11729816DOI: 10.21037/atm-24-109Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explains a study conducted to understand the connections between obesity, changes in gut microbiome, and gene expression changes in joints, which are associated with the development of osteoarthritis in horses.

Overview of the Study

  • The study’s main objective was to compare the fecal microbiome in healthy horses and horses with obesity-induced osteoarthritis (OA). The researchers also sought to correlate the changes in the fecal microbiome with changes in gene expression in synovial fluid cells, circulating leukocytes, and cytokine levels in the plasma and synovial fluid.
  • The subjects of the study were 18 adult horses – 12 were healthy, and 6 had osteoarthritis. The horses’ osteoarthritis status was confirmed via lameness evaluation, response to intra-articular diagnostic analgesia, and radiographic and arthroscopic evidence.
  • The study involved the isolation of fecal matter, peripheral blood mononuclear cells (PBMCs), and synovial fluid cells from both healthy and osteoarthritic horses.

Finding Connections between Obesity, Gut Microbiome, and Osteoarthritis

  • The researchers found that horses with osteoarthritis had higher body condition scores (P=0.009) and elevated levels of certain cytokines in both plasma and synovial fluid. These cytokines include IL-2, IL-6, IL-18, IFN-γ, IP-10, G-CSF in plasma and IL-1β, IL-6, IL-17A, IL-18, IP-10, G-CSF in synovial fluid, indicating a more pronounced immune response in OA horses.
  • Further, analysis of the fecal microbial DNA revealed distinct differences in the gut microbiome between healthy and OA-affected horses. The gut microbiome diversity was found to be reduced in OA horses, and the relative abundance of microbial taxa was different in OA horses compared to the healthy ones.
  • These changes in the gut microbiome were linked to differences in gene expression related to cell structure, extracellular matrix, collagen, laminin, migration, and motility, and the immune response to inflammation in the OA joints.

Conclusions from the Study

  • The study presented significant findings implying a direct link between obesity, alterations in the gut microbiome, and differential gene expression in joints associated with the development of osteoarthritis.
  • This correlation sets a foundation for future therapeutic studies targeting the gut microbiome for the treatment or prevention of osteoarthritis.

Cite This Article

APA
Chow L, Kawahisa-Piquini G, Bass L, Hendrickson D, Patel A, Rockow M, Dow S, Pezzanite LM. (2024). Correlation of fecal microbiome dysregulation to synovial transcriptome in an equine model of obesity associated osteoarthritis. Ann Transl Med, 12(6), 112. https://doi.org/10.21037/atm-24-109

Publication

Annals of translational medicine
ISSN: 2305-5839
NlmUniqueID: 101617978
Country: China
Language: English
Volume: 12
Issue: 6
Pages: 112

Researcher Affiliations

Chow, Lyndah
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Kawahisa-Piquini, Gabriella
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Bass, Luke
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Hendrickson, Dean
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Patel, Ashana
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Rockow, Meagan
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Dow, Steven
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Pezzanite, Lynn M
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.

Conflict of Interest Statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-24-109/coif). L.M.P. reports that this study was funded by the Animal Health and Disease Grant (No. NI22AHDRXXXXG011) Project Accession No. 7003828 from the USDA National Institute of Food and Agriculture. Additional grant and contract funding sources include Grayson Jockey Club Research Foundation, NIH/NCATS CCTSI and the CSU Research Council. Current or pending patents unrelated to this work include CSU-SURF 2022-041, CSU-SURF 2021-053, CSU SURF 2023-025, and CSU STRATA 2024-016. The other authors have no conflicts of interest to declare.

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