Manipulation of the gut microbiome as a strategy to treat the osteoarthritis of obesity

Obesity is a risk factor for Osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic inflammation, now understood to be caused by an altered gut microbiome. Oligofructose, a non-digestible prebiotic fiber, can correct the obese gut microbiome, suggesting a novel approach to treat the OA of obesity. Here we report that in the obese murine gut, beneficial Bifidobacteria are lost while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with accelerated knee OA. Oligofructose supplementation corrects the obese gut microbiome in part by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This leads to reduced inflammation in the colon, circulation and knee, and protection from OA. This novel recognition of a gut microbiome-OA connection sets the stage for discovery of new OA therapeutics targeting specific microbes inhabiting the intestinal space to inhibit disease pathology.

肥胖是骨关节炎（Osteoarthritis, OA）的危险因素，而骨关节炎是美国最主要的致残病因。肥胖对骨关节炎的影响由全身性炎症所介导，而目前学界认为该全身性炎症源于失调的肠道微生物组（gut microbiome）。低聚果糖（Oligofructose）作为一种不可消化的益生元纤维，可纠正肥胖相关的肠道微生物组紊乱，为治疗肥胖相关性骨关节炎提供了全新策略。本研究发现，在肥胖小鼠的肠道中，有益的双歧杆菌属（Bifidobacteria）丰度显著降低，而关键促炎菌种的数量则大幅增加。这种下游的全身性炎症反应最终会导致膝骨关节炎病情加速进展。补充低聚果糖可通过维持关键共生菌群（尤其是假长双歧杆菌（Bifidobacterium pseudolongum））的丰度，部分纠正肥胖小鼠的肠道微生物组失衡。该作用可减轻结肠、循环系统及膝关节的炎症反应，进而对骨关节炎起到保护作用。这项关于肠道微生物组与骨关节炎关联的全新发现，为开发靶向肠道特定微生物以抑制疾病病理进程的新型骨关节炎治疗药物奠定了重要基础。