Abstract
Kashin-Beck disease (KBD) is a severe osteochondral disorder that may be driven by the interaction between genetic and environmental factors. We aimed to improve our understanding of the gut microbiota structure in KBD patients of different grades and the relationship between the gut microbiota and serum metabolites. Fecal and serum samples collected from KBD patients and normal controls (NCs) were used to characterize the gut microbiota using 16S rDNA gene and metabolomic sequencing via liquid chromatography-mass spectrometry (LC/MS). To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria in the KBD patients, metagenomic sequencing of fecal samples from grade I KBD, grade II KBD and NC subjects was performed. The KBD group was characterized by elevated levels of Fusobacteria and Bacteroidetes. A total of 56 genera were identified to be significantly differentially abundant between the two groups. The genera Alloprevotella, Robinsoniella, Megamonas, and Escherichia_Shigella were more abundant in the KBD group. Consistent with the 16S rDNA analysis at the genus level, most of the differentially abundant species in KBD subjects belonged to the genus Prevotella according to metagenomic sequencing. Serum metabolomic analysis identified some differentially abundant metabolites among the grade I and II KBD and NC groups that were involved in lipid metabolism metabolic networks, such as that for unsaturated fatty acids and glycerophospholipids. Furthermore, we found that these differences in metabolite levels were associated with altered abundances of specific species. Our study provides a comprehensive landscape of the gut microbiota and metabolites in KBD patients and provides substantial evidence of a novel interplay between the gut microbiome and metabolome in KBD pathogenesis.
Highlights
Kashin-Beck disease (KBD) is an endemic degenerative osteochondrosis with irreversible pathological and clinical development, including shortened and enlarged fingers, deformed limb joints, and limited movement [1, 2]
Accumulating evidence suggest that cartilage damage in patients with KBD is driven by the interaction between genetic and environmental factors [8]
Alterations in gut microbiota composition in patients with receiver operating characteristic (ROC) curves and computed the KBD based on 16S rDNA data area under the curve (AUC) values
Summary
Kashin-Beck disease (KBD) is an endemic degenerative osteochondrosis with irreversible pathological and clinical development, including shortened and enlarged fingers, deformed limb joints, and limited movement [1, 2]. The processes involving metabolism, apoptosis, adaptive immune defense, the cytoskeleton, cell movement, and extracellular matrix turnover [3,4,5,6,7] have been found to play key roles during chondrocyte injury in KBD, there are currently no clear underlying mechanisms involved in the occurrence and development of KBD, effective treatment options are very limited. It has been suggested that changes in the gut microbiome composition and metabolic activity can modify the immune response and metabolite levels, leading to constant low-grade inflammation can lead to cartilage injury and frailty [9, 10]. The role of the microbiome in cartilage health is considered important and the study of this new cartilage-gut-microbiome axis will undoubtedly lead to new treatment options for joint diseases such as KBD. A number of studies have shown that many microbial metabolites could affect the development of osteochondral disease [11, 12], suggesting that a diverse gut microbiome could affect an improvement in the metabolic relationship between gut microbes and their hosts [13]
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