Multiomics analyses identify diet-derived creatine and α-linolenic acid linking with metastatic thyroid cancer.
BACKGROUND Thyroid cancer (TC) has traditionally been regarded as an indolent malignancy. However, it retains the potential for metastasis and lethality, underscoring its status as a malignant tumor. To explore the interplay between serum metabolite profiles, gut microbial communities, and TC metastasis, we conducted a comprehensive study. METHODS Serum metabolites were analyzed using untargeted metabolomics methods to characterize the metabolic changes. Two diet-derived metabolites, creatine (Cr) and α-linolenic acid (ALA), were selected for in vitro validation. Finally, 16S rRNA gene sequencing was used to characterize the intestinal microbial composition and analyze the correlation between differential metabolites and differential intestinal microbiota. RESULTS LC-MS analysis of serum metabolites identified Arginine and proline metabolism and Arginine biosynthesis as the primary metabolic pathways altered in TC metastasis. Both Cr and ALA effectively inhibited EMT, migration, and invasion of TC cell lines, TPC1 and FTC-133. The analysis of gut microbiota composition revealed that Cr and ALA showed significant correlations with the bacteria genera, Porphyromonas and Papillibacter. CONCLUSIONS This study highlights that TC metastasis is associated with significant alterations in the serum metabolite profiles of patients, and Cr and ALA play a role in inhibiting TC development. Furthermore, Cr and ALA were correlated with Porphyromonas and Papillibacter, implying their potential link with food-borne components and their connected impact on TC metastasis. The findings provide new insights into the role of metabolites and gut microbiota in TC progression, suggesting novel avenues for dietary intervention in cancer treatment.