Effects of Exercise on Gut Microbiome and Serum Metabolomics in Post-Traumatic Osteoarthritis Rats

Abstract

Objective: The aim of this work is to investigate the impact of exercise on gut microbiome composition, serum metabolites, and their correlation with osteoarthritis (OA) severity. Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into four groups: Sham rats without treadmill walking (Sham/Sed group, n = 9), Sham rats with treadmill walking 2 months (Sham/TW2M group, n = 9), PTOA rats without treadmill walking (PTOA/Sed group, n = 9), and PTOA rats with treadmill walking 2 months (PTOA/TW2M group, n = 9). The PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and destabilization of the medial meniscus (DMM). Histological evaluation and micro-CT analysis were performed to observe the pathological changes in cartilage and subchondral bone, respectively. Additionally, we conducted 16S rDNA sequencing of fecal samples and untargeted metabolomic analysis using liquid chromatography–mass spectrometry (LC–MS) of serum samples to detect the alteration of gut microbiota composition and metabolites. Results: Exercise effectively mitigated OA-related pathological changes, including articular cartilage degeneration and subchondral bone loss. Moreover, 16S rDNA sequencing analysis of gut microbiome revealed a decreased abundance of Bacteroidetes (p Bacteroidia (p Rikenellaceae (p Paraprevotellaceae] (p Paraprevotella (p Firmicutes (p Rikenellaceae significantly positively correlated with both OARSI (r = 0.81, p p p p Conclusions: Exercise can effectively mitigate OA through slowing down articular cartilage degeneration and subchondral bone loss, modulating gut microbiota composition, and increasing beneficial metabolites.

Keywords

• osteoarthritis
• exercise
• gut–joint axis
• metabonomics