Abstract
Background: Kashin-Beck disease (KBD) is a distinct osteoarthropathy in China with an unclear pathogenesis. This study aims to explore whether perturbations in the intestine metabolome could be linked to KBD individuals. Methods: An investigation was conducted in KBD endemic villages and fecal samples were collected. After applying inclusion and exclusion criteria, a total of 75 subjects were enrolled for this study, including 46 KBD (including 19 Grade I KBD and 27 Grade II KBD) and 29 controls. Untargeted metabolomics analysis was performed on the platform of UHPLC-MS. PLS-DA and OPLS-DA were conducted to compare the groups and identify the differential metabolites (DMs). Pathway analysis was conducted on MPaLA platform to explore the functional implication of the DMs. Results: Metabolomics analysis showed that compared with the control group, KBD individuals have a total of 584 differential metabolites with dysregulated levels such as adrenic acid (log(2)FC = -1.87, VIP = 4.84, p = 7.63 × 10(-7)), hydrogen phosphate (log(2)FC = -2.57, VIP = 1.27, p = 1.02 × 10(-3)), taurochenodeoxycholic acid (VIP = 1.16, log(2)FC = -3.24, p = 0.03), prostaglandin E3 (VIP = 1.17, log(2)FC = 2.67, p = 5.61 × 10(-4)), etc. Pathway analysis revealed several significantly perturbed pathways associated with KBD such as selenium micronutrient network (Q value = 3.11 × 10(-3), Wikipathways), metabolism of lipids (Q value = 8.43 × 10(-4), Reactome), free fatty acid receptors (Q value = 3.99 × 10(-3), Reactome), and recycling of bile acids and salts (Q value = 2.98 × 10(-3), Reactome). Subgroup comparisons found a total of 267 differential metabolites were shared by KBD vs. control, KBD II vs. control, and KBD I vs. control, while little difference was found between KBD II and KBD I (only one differential metabolite detected). Conclusions: KBD individuals showed distinct metabolic features characterized by perturbations in lipid metabolism and selenium-related bioprocesses. Our findings suggest that the loss of nutrients metabolism balance in intestine was involved in KBD pathogenesis. Linking the nutrients metabolism (especially selenium and lipid) to KBD cartilage damage should be a future direction of KBD study.