Characterizing gut microbiota and fecal metabolites in intervertebral disc degeneration: insights into the gut-disc...

This study aims to delineate the characteristic profiles of gut microbiota and fecal metabolites in individuals diagnosed with intervertebral disc degeneration (IDD), potentially elucidating the gut-disc axis as a novel perspective for understanding IDD pathophysiology.

Fecal samples were collected from 15 patients diagnosed with IDD, classified according to the Pfirrmann grading system, with a distribution of three individuals per grade. Additionally, samples were obtained from five healthy controls for comparative analysis. 16S rDNA sequencing was employed to analyze gut microbiota composition, while liquid chromatography-mass spectrometry was used for untargeted metabolite profiling. Distinct gut microbiota signatures were observed in IDD patients compared to controls, characterized by a dysbiotic state with increased biodiversity. More importantly, patients with IDD exhibit a higher abundance of Proteobacteria and Fusobacteriota, along with reduced abundances of Campilobacterota and Synergistota at the phylum level, as determined by Linear Discriminant Analysis Effect Size (LEfSe). Fecal metabolite analysis revealed an altered metabolic profile in IDD patients, including aggrandized levels of lipids and lipid-like molecules, which are associated with oxidative stress and tissue degradation. KEGG pathways identified five significant ones, including Nucleotide metabolism, Taurine and hypotaurine metabolism, Arginine and proline metabolism, Carbohydrate digestion and absorption, and FoxO signaling pathway. Together with receiver operating characteristic analysis, our data indicate that the upregulation of Permethrin and the reduction of 3ccPA, Thymine, His-ser, Hypoxanthine, N6-Acetyl-L-lysine, Safranin, and Peimine are highly associated with IDD.

Our findings suggest a strong association between gut microbiota dysbiosis and fecal metabolite alterations in the pathogenesis of IDD.