Distinct stage-specific phenotypes of gut microbiota and metabolites associated with vitamin levels in thyroid cancer

Increasing evidence suggests the human gut ecosystem and circulating vitamin levels are potentially associated with differentiated thyroid cancer (TC) development. This study aimed to investigate stage-specific signatures of microbiota, metabolites, and vitamin levels in TC. Fecal microbial and metabolic sequencing, with serum vitamin detection, was performed on samples from 129 TC patients, 14 patients with thyroid nodules (TNs), and 22 healthy controls (HCs). Alterations in the microbiome and metabolome were observed in TN and TC cases across all stages of tumor progression. First, the relative abundances of Erysipelatoclostridium , Eubacterium_eligens_group , Ruminococcus_2 , and Ruminococcus_gnavus_group increased significantly from TN to the more advanced stages of TC. Second, Faecalibacterium and Butyricicoccus , involved in short-chain fatty acid production, decreased significantly as the tumor progressed. Metabolomic analyses revealed that most differential metabolites associated with central carbon metabolism in cancer, amino acid metabolism, and vitamin digestion and absorption pathways were significantly increased. Conversely, some metabolites involved in vitamin digestion and absorption pathways were significantly reduced in TC compared with those in HCs. Furthermore, serum vitamin analyses revealed significantly decreased levels of vitamins C, D, D 2 , and D 3 in TC patients. Complex co-occurrence patterns among the identified bacteria, metabolites, and vitamins were observed and possibly correlated with TC severity. Potential microbial and metabolic markers capable of discriminating among TN, TC, and HC groups were also preliminarily explored. This multi-omics analysis of a tumor progression cohort suggests alterations in the intestinal microecology might occur in the early stages of TC development. These findings have important etiological and diagnostic implications.