Translational Research in Pain, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill.
Arthritis Rheumatol. 2024 Dec;76(12):1758-1763. doi: 10.1002/art.42956. Epub 2024 Aug 9.
The purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model.
Fecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA-pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray-Curtis distance matrices. All downstream analyses were completed in R.
No significant differences between healthy and OA-pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score.
Similar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti-inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.
本研究旨在利用宠物犬这一具有临床相关性的转化模型,增强人们对肠道微生物组与骨关节炎(OA)及其相关疼痛之间关系的现有认识。
采集了 93 只家养宠物犬的粪便样本。采用经过验证的方法,将犬分为临床健康或 OA 疼痛组。通过 Illumina NovaSeq 平台进行 shotgun 测序进行宏基因组分析。使用 MetaPhlAn2 和 HUMAnN2 评估细菌分类和途径的相对丰度。对健康组和 OA 疼痛组分别使用非参数检验对每个分类群进行比较,采用 Benjamini 和 Hochberg 进行多重比较调整。使用 Bray-Curtis 距离矩阵进行置换方差分析。所有下游分析均在 R 中完成。
健康犬和 OA 疼痛犬的 alpha 和 beta 多样性均无显著差异。我们发现了 13 个与 OA 病例状态具有名义显著(P < 0.05)关联的分类群,但在进行多重比较调整后,没有一个关联仍然显著。疼痛严重程度、移动性或活动水平、年龄或体成分评分与 alpha 或 beta 多样性或厚壁菌门与拟杆菌门比值均无差异。
与最近在人类中进行的研究类似,本研究未发现 OA 疼痛犬和健康对照组犬之间粪便微生物群落存在显著差异。在这种自然发生的模型中,未来的研究应扩展这些数据,并将肠道微生物组与肠道通透性以及循环促炎和抗炎分子相关联,以更好地了解肠道微生物组对 OA 和 OA 疼痛的影响。