Metagenomic analysis of gut microbiota and its correlation with thyroid hormones in papillary thyroid cancer before and after operation

BACKGROUND: The changes of intestinal flora and thyroid hormone levels before and after operation for papillary thyroid cancer (PTC) and their relationship are not clear. It may interfere with the intestinal thyroid axis, change the systemic thyroid hormone regulation and exogenous treatment response. It is recognized that this microbial involvement is clinically related to long-term metabolic outcomes, and future strategies for microbial targeted adjuvant therapy are suggested. This study aims to provide direct evidence and a comprehensive understanding of the relationship between intestinal flora and thyroid hormone levels before and after surgical treatment of papillary thyroid cancer through metagenomic analysis. METHODS: As a paired before and after observation study, 20 patients diagnosed with papillary thyroid cancer were included in the study. Fecal samples and thyroid hormone levels were collected within 3 days before operation and 72 hours after operation. First, the intestinal microbiota of these 20 patients was analyzed for metagenomic differences, such as α and β diversity analysis, PCoA, ANOSIM, Spearman correlation analysis, FDR correction, KEGG pathway enrichment and correlation network analysis. Subsequently, the changes of hormone levels were examined in combination with the collected intestinal microbiota. RESULTS: There were significant differences in the diversity and composition of the gut microbiota in patients with papillary thyroid cancer before and after surgery. At the species level, the eight most significantly different groups identified were Bacteroides sp., Clostridium sp., Bacteroides fragilis, Alistipes sp., Parabacteroides sp., Bacteroides thetaiotaomicron, Phocaeicola dorei, and Oscillibacter sp. Notably, Clostridium sp. higher abundance in the pre-operative group, whereas Bacteroides sp., Bacteroides fragilis, Alistipes sp., Parabacteroides sp., Phocaeicola sp., and Bacteroides thetaiotaomicron were more prevalent in the post-operative group. After operation, FT4 showed an upward trend, while TSH, PTH and HTG showed a downward trend. The primary differential pathways associated with these changes pertained to iron uptake and regulation, polysaccharide utilization and transport, as well as metabolism and stress response. The pre-operative group was predominantly involved in ribosome biosynthesis, along with amino acid synthesis for valine and leucine. In contrast, the post-operative group primarily engaged in lipoic acid metabolism, glycosaminoglycan degradation, and bacterial secretion systems. CONCLUSION: This study found that the composition, diversity and function of intestinal flora changed in patients with papillary thyroid cancer after operation. Specific microbial taxa may be associated with fluctuations in thyroid hormone levels. In the future, regulating intestinal flora can be used as an adjuvant therapy for hormone regulation in patients undergoing PTC surgery.