O-Sullivan InSug, Natarajan Anbazhagan Arivarasu, Singh Gurjit, Ma Kaige, Green Stefan J, Singhal Megha, Wang Jun, Kumar Anoop, Dudeja Pradeep K, Unterman Terry G, Votta-Velis Gina, Bruce Benjamin, van Wijnen Andre J, Im Hee-Jeong
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60612, USA.
Biomedicines. 2022 Jun 1;10(6):1298. doi: 10.3390/biomedicines10061298.
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD).
为了测试益生菌疗法对骨关节炎(OA)的疗效,我们在通过部分内侧半月板切除术(PMM)诱导OA后,通过口服灌胃(每周2次)给予嗜酸乳杆菌(LA)。通过von Frey细丝和热板试验评估疼痛。通过番红O/固绿染色、免疫荧光显微镜和RT-qPCR对膝关节、脊髓、背根神经节和远端结肠的关节病理学和疼痛标志物进行了全面分析。LA可急性减轻炎症性膝关节疼痛,并防止OA进一步发展。我们检测的组织中软骨降解酶、疼痛标志物和炎症因子的显著减少支持了LA的治疗效果。这一发现表明LA对OA可能具有临床疗效。通过16S rRNA基因扩增子测序分析评估了LA治疗对粪便微生物群的影响。与载体处理的小鼠相比,LA显著改变了粪便微生物群(PERMANOVA p < 0.009)。我们的临床前OA动物模型显示,LA具有显著的OA疾病改善作用,表现为关节疼痛迅速减轻、软骨保护和失调逆转。我们的研究结果表明,LA治疗具有有益的全身作用,有可能开发成为一种安全的OA疾病改善药物(OADMD)。