AUTHOR=Xu Tianyang , Yang Dong , Liu Kaiyuan , Gao Qiuming , Liu Zhongchen , Li Guodong TITLE=Miya Improves Osteoarthritis Characteristics via the Gut-Muscle-Joint Axis According to Multi-Omics Analyses JOURNAL=Frontiers in Pharmacology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.816891 DOI=10.3389/fphar.2022.816891 ISSN=1663-9812 ABSTRACT=Background: Gut microbiota (GM) is associated with osteoarthritis (OA) progression, and Miya (MY) is a product made from Clostridium Butyricum. This study aimed to investigate the effects of MY on OA, and its related mechanisms. Methods: An OA rat model was established, and then MY was used to treat with the rats for four weeks. Afterwards, the knee joint samples were stained with hematoxylin-eosin (HE), and feces samples in the OA and OA+MY groups were sent for 16s rDNA sequencing and metabolomic analysis. After that, the contents of succinate dehydrogenase (SDH) and muscle glycogen (MG) in tibia muscle were determined, and the related genes and proteins were detected by RT-qPCR and western blot. Results: HE staining showed that MY treatment could alleviate the symptoms of OA. After sequencing, MY significantly increased Chao1, Shannon and Pielou’s evenness values compared with the OA group. At genus level, the abundance of Prevotella, Ruminococcus, Desulfovibrio, Shigella, Helicobacter, and Streptococcus was higher in the OA group; whereas Lactobacillus, Oscillospira, Clostridium, and Coprococcus were enriched after MY treatment. Through metabolomic analysis, a total of 395 differential metabolites were identified. Additionally, MY treatment significantly increased SDH and MG contents in muscle caused by OA (P > 0.05). Finally, AMPK, Tfam, Myod, Ldh, Chrna1, Chrnd, Rapsyn and Agrin were significantly down-regulated in the muscle of OA mice, and Lcad, Mcad and IL-1β were up-regulated; whereas MY could significantly reverse their levels induced by OA. Conclusions: MY may promote joint damage repair and protect OA via gut-muscle-joint axis.