Background/Purpose: The destabilization of the medial meniscus (DMM) model is widely used in murine OA research due to its reproducibility and ability to recapitulate key features of human disease, particularly in the central weight-bearing regions of the medial tibial plateau and femoral condyle. While the role of the gut microbiome in OA pathogenesis is increasingly recognized, with mounting evidence linking gut dysbiosis to musculoskeletal outcomes, the impact of DMM-induced OA on the gut microbiota-and whether similar shifts occur following sham surgery-remains insufficiently characterized. This study addresses this gap by systematically evaluating gut microbiome changes following DMM and sham interventions in mice.

Methods: Male (N = 59) and female (N = 14) B6 mice underwent either DMM or sham surgery (skin, fascia, and joint capsule opened but no meniscus transection) at 12 weeks of age. Biological samples in the form of cecal contents were collected at 4 weeks, 8 weeks, and 12 weeks after surgical intervention. Bacterial DNA was isolated from these samples and subjected to 16S rRNA gene sequencing using an Illumina MiSeq sequencer. The obtained data were analyzed using the Qiime2 workflow. Group comparisons were determined using LEfSe analysis, with a 95% confidence interval after taxonomic assignment by alignment to the Greengenes2 dataset. Differences among bacterial groups were assessed using the Mann-Whitney U test.

Results: In a comparison between DMM and Sham samples, data reveals shift in microbiota composition. Specifically, the Sham group exhibited significant enrichments (p< 0.005) in Clostridia_258483 (Christensenellales, CAG_552), Oscillospirales (p< 0.002) including Acutalibacteraceae, Oscillospiraceae_88309, and Ruminococcaceae, as well as TANB77 (CAG_508) and Bacilli (RF39, Turicibacter). Conversely, the DMM group showed significant enrichments in Oscillospirales (p< 0.002) including Oscillospiraceae_88309 and Ruminococcaceae, TANB77 (p< 0.05) including CAG_508, and Bacilli (p< 0.05) including RF39 and UBA660. Additional comparisons revealed that DMM vs Control groups showed significant increases in Bacteroidota (p< 0.002) including Bacteroidia, Rikenellaceae, and Muribaculaceae, Oscillospirales (p< 0.002) including Acutalibacteraceae, and Bacilli (p< 0.05) (Erysipelotrichales and Coprobacillaceae), while no significant differences were observed between Sham and Control mice.

Conclusion: Our data underscore a modulatory role for the gut microbiota in OA progression while confirming that brief surgical trauma alone does not perturb the intestinal microbial community. Mapping these gut–joint interactions may unveil novel microbiome-targeted strategies for OA treatment. Ongoing and future work to dissect the mechanistic links and long-term effects of dysbiosis will be critical to advancing our understanding of OA pathogenesis and guiding precision therapies.

Figure 1: Differential microbiome clades between DMM and sham surgery

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/specific-gut-microbiome-remodeling-occurs-after-induction-of-oa-via-dmm-surgery-compared-to-sham-surgery/