Gut microbiota is associated with response to (131)I therapy in patients with papillary thyroid carcinoma

PURPOSE: Radioactive iodine ((131)I) therapy is a conventional post-surgery treatment widely used for papillary thyroid carcinoma (PTC). Since (131)I is orally administered, we hypothesize that it may affect gut microbiome. This study aims to investigate alterations of intestinal microbiome caused by (131)I therapy in PTC patients and explore its association with response to (131)I therapy. METHODS: Fecal samples of 60 PTC patients pre- and post-(131)I therapy were collected to characterize the (131)I therapy-induced gut microbiota alterations using 16S rRNA gene sequencing. According to the inclusion criteria, sequence data of 40 out of the 60 patients, divided into excellent response (ER) group and non-excellent response (NER) group, were recruited to investigate the possible connection between gut microbiota and response to (131)I therapy. Multivariate binary logistic regression was employed to construct a predictive model for response to (131)I therapy. RESULTS: Microbial richness, diversity, and composition were tremendously altered by (131)I therapy. A significant decline of Firmicutes to Bacteroides (F/B) ratio was observed post-(131)I therapy. (131)I therapy also led to changes of gut microbiome-related metabolic pathways. Discrepancies in β diversity were found between ER and NER groups both pre- and post-(131)I therapy. Furthermore, a predictive model for response to (131)I therapy with a p value of 0.003 and an overall percentage correct of 80.0% was established, with three variables including lymph node metastasis, relative abundance of g_Bifidobacterium and g_Dorea. Among them, g_Dorea was identified to be an in independent predictor of response to (131)I therapy (p = 0.04). CONCLUSION: For the first time, the present study demonstrates the gut microbial dysbiosis caused by (131)I therapy in post-surgery PTC patients and reveals a previously undefined role of gut microbiome as predictor for (131)I ablation response. G_Dorea and g_Bifidobacterium may be potential targets for clinical intervention to improve response to (131)I in post-operative PTC patients. TRIAL REGISTRATION: ChiCTR2100048000. Registered 28 June 2021.