Distinct Thyroid Tissue Microbiota Profiles in Papillary Thyroid Carcinoma: A Prospective Study

Background: Gut–thyroid crosstalk has been implicated in endocrine homeostasis, yet intratumoral microbiota in papillary thyroid carcinoma (PTC) and its relationship to the gut remain underexplored. This pilot study profiled matched tumor and adjacent non tumor thyroid tissues together with stool to define tissue specific microbial signatures in Turkish patients with PTC. Methods: In this prospective study, adults undergoing thyroidectomy for PTC provided preoperative stool and, intraoperatively, paired tumor and adjacent non tumor thyroid tissue. Microbiota were characterized by 16S rRNA gene sequencing (Ion Torrent). Diversity metrics, differential abundance (paired tests), effect sizes (r) and 95% CIs were reported with Benjamini–Hochberg false discovery rate (FDR) correction. Results: Fifteen patients were enrolled (13 female; mean age 43.0 ± 10.5 years). Compared with non tumor tissue, tumor tissue exhibited enrichment of Streptococcaceae, Clostridiaceae (both q=0.011), as well as nominal enrichment of Acetobacteraceae (q=0.084) and Bifidobacteriaceae (q=0.236). At the genus level, Neisseria (q=0.005), Streptococcus (q=0.032), Prevotella (q=0.008), and Lactobacillus (q=0.005) were enriched in tumor tissue, while Butyricimonas (q=0.005) was depleted. At the species level, Cutibacterium (Pro-pionibacterium) acnes was nominally higher in tumor tissue (p=0.045; q=0.900). Stool profiles differed markedly from thyroid tissues and showed limited concordance with intrathyroidal signatures. Limitations: The small sample size, absence of healthy tissue or stool controls, and reliance on 16S rRNA sequencing limit the generalizability and functional interpretation of these findings. Conclusions: PTC harbors a distinct intra-tumoral microbiota partially overlapping with the gut but characterized by specific tumor associated taxa. These findings support a microbiota–thyroid cancer axis and mo-tivate larger, multi omic studies for biomarker and therapeutic exploration