低聚果糖改善肠道菌群，可治疗与肥胖相关的骨关节炎
Title：
Targeting the gut microbiome to treat the osteoarthritis of obesity
Abstract：
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, and increased systemic inflammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic fiber, can restore a lean gut microbial community profile in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that - compared with the lean murine gut - obesity is associated with loss of beneficial Bifidobacteria, while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This is associated with reduced inflammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome-OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of specific microbial species inhabiting the intestinal space.
All Authors：
Eric M Schott,Christopher W Farnsworth,Alex Grier,Jacquelyn A Lillis,Sarah Soniwala,Gregory H Dadourian,Richard D Bell,Madison L Doolittle,David A Villani,Hani Awad,John P Ketz,Fadia Kamal,Cheryl Ackert-Bicknell,John M Ashton,Steven R Gill,Robert A Mooney,Michael J Zuscik
First Authors：
Eric M Schott
Correspondence：
Michael J Zuscik
摘要：
对比胖瘦小鼠的肠道菌群，发现肥胖与有益的双歧杆菌缺失、消化链球菌科和消化球菌科中的促炎菌种增多相关；肥胖相关的肠道菌群失调，伴随巨噬细胞向膝关节滑膜迁移，加剧创伤性膝骨关节炎；给肥胖小鼠补充低聚果糖（OF）虽无法缓解高脂饮食诱导的肥胖，但可改善小鼠肠道菌群，尤其是增加假长双歧杆菌；OF改善肠道菌群，与肥胖小鼠的结肠、循环和膝关节的炎症减轻相关，抑制肥胖症关节损伤中的分子、细胞和关节结构改变。