Characterization of microbiota dysbiosis in papillary thyroid carcinoma and benign thyroid nodules: low abundance of intestinal butyrate-producing bacteria.

backgroundThe thyroid-gut axis refers to the intricate relationships among the gut, intestinal microbiota, and thyroid gland, and it is speculated to play an important role in the development of thyroid diseases. The aim of this study was to identify the differentiated bacteria in the intestinal microbiota associated with papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTNs) to offer potential avenues for further exploration and therapeutic interventions.

methodsFaecal microbiotas of 197 subjects (73 from subjects with BTNs, 62 from subjects with PTC, and 62 from sex- and age-matched controls) were characterized by sequencing the V3-V4 region of 16 S rDNA using the Illumina NovaSeq 6000 platform. Microbiomics and machine learning-assisted approaches were used to identify the PTC-/BTN-associated intestinal microbial indicators.

resultsCompared with the abundance of coabundant groups (CAGs) in the PTC, BTN, and control groups, the abundance of two Genus-CAGs consisting of butyrate producers, such as Blautia, Lachnoclostridium, Lachnospiraceae_unclassified, Eisenbergiella, Flavonifractor and Hungatella, was lower in the PTC group than in the control group. In particular, both ANCOM-BC2 and Wilcoxon rank-sum test results consistently demonstrated significant enrichment of the butyrate-producing genera Oscillibacter, Coprobacter, and Colidextribacter in both BTN patients and healthy controls. The majority of discriminatory amplicon sequence variants (ASVs) that could discriminate PTCs from controls, as well as from BTNs, were from Prevotella, Streptococcus, Bacteroides, and butyrate-producing groups, such as the Oscillibacter, Lachnospiraceae, and Christensenellaceae (R7) groups. ASV indicators from Prevotella and Streptococcus were most abundant in the PTC group, and those from Bacteroides and the butyrate-producing/-promoting group were least abundant in the PTC group. Additionally, the ASVs that could discriminate the BTN group from the control group, as well as PTC group included other butyrate-producing groups, the Clostridium_sensu_stricto group, and the Eubacterium_siraeum group.

conclusionsThis study demonstrates that dysbiosis linked to thyroid nodules is marked by a substantial decline in intestinal butyrate-producing and butyrate-promoting taxa. Future work to confirm these results should include shotgun metagenomic sequencing paired with quantitative analyses of gene abundance and expression to fully ascertain the functional implications.