Background/Purpose: Mounting evidence suggests that gut microbiome shifts may be associated with knee osteoarthritis (OA) development. We have previously shown that gut microbiome transplantation from OA-resistant MRL/MpJ mice into OA-susceptible B6 mice results in robust protection against OA development. In the present study, we evaluated genus Acomys (African spiny mice), also previously shown to be resistant to OA.

Methods: Fresh frozen cecal content from 7 adult male spiny mice was obtained from the University of Kentucky colony (Dr. Seifert). Under sterile conditions, cecal content was diluted in 200uL of 50:50 sterile glycerol and PBS then transplanted via oral gavage into n=8 11-week-old B6 non-Germ-free (SPF) male mice and n=4 11-week-old C57BL6 (B6) Germ-free (GF) male mice in the OMRF gnotobiotic facility. One week later, unilateral destabilization of the medial meniscus (DMM) surgery was performed. Control groups included n=7 B6-SPF-microbiota-into-male GF mice, n=10 male B6-SPF mice, and n=6 male B6-GF mice. Mice were euthanized 8 weeks after DMM and submitted for OARSI histopathologic scoring. For microbiome analysis, cecal DNA was extracted, 16S rRNA gene amplification done, initial analysis performed via QIIME2 amplicon v.2024-10, aligned to the GreenGenes2 reference tree, and differential microbiome analysis performed using Maaslin2 (v.1.16.0). We also analyzed similarities to our previous histologic and microbiome studies of the OA-protected MRL/MpJ mouse strain (n=5 SPF MRL-into-B6 GF, n=12 SPF MRL-into-B6).

Results: Gut microbiome transplantation from spiny mice to SPF B6 mice prior to DMM surgery resulted in substantial protection from histologic OA development (spiny-into-B6 2.9±0.8 vs. B6 control 7.8±0.5, mean summed OARSI score±SEM, P=0.0003, Figure 1A, 1B). We then confirmed this finding by transplanting gut microbial content from spiny mice to GF B6 mice (ordinarily OA protected), where spiny transplantation induced mild OA susceptibility, whereas wild-type B6 cecal transplant did induce OA susceptibility (spiny-into-GF 2.3±0.3, GF control 1.5±0.3, B6-into-GF 11.2±0.9, P=0.053 spiny-into-GF vs. GF control, P=0.003 spiny-into-GF vs. B6-into-GF). In microbiome analysis, substantial differences were present between spiny mice and B6 mice (n=75 differences, q≤0.05). These differences were substantially similar to our previously published MRL-into-B6 transplantation experiments (n=29 in current reanalysis), Figure 2. Indeed, 13 of these microbiome clades were shared in both comparisons, and 11 were similar in direction and magnitude of change (increased in MRL were all increased in spiny and vice-versa).

Conclusion: The gut microbiome of OA-protected spiny mice confers OA protection in wild-type mice following microbiome transplantation. Microbiome differences in spiny mice are largely similar to previous studies of another OA protected strain, MRL/MpJ. Future work should evaluate whether spiny mouse microbiome transplantation also confers OA pain/behavioral protection and the degree to which individual microbiome species contribute to these findings.

Figure 1: Histologic OA outcomes following microbiome transplantation and DMM

Figure 2: Cecal microbiome 16S analysis, clade difference overlaps in Spiny (Acomys) vs. B6 and MRL/MpJ vs. B6

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/oa-protection-in-african-spiny-acomys-mice-is-partially-mediated-by-the-gut-microbiome-and-is-transferrable-to-wild-type-mice-via-microbiome-transplantation/