Microbial biomarkers and sex-associated gut microbiota characteristics of thyroid cancer

Microbial biomarkers have emerged as promising tools for early cancer detection and disease monitoring. This study aimed to investigate microbial biomarkers and sex-associated differences in gut microbiota associated with thyroid cancer (TC). A total of 268 participants were recruited: 60 females with TC, 26 males with TC, and 182 healthy controls. The patient and healthy groups were comparable in terms of age and sex ratio. We first compared the gut microbiota between the patients and healthy participants, followed by sex-specific analyses: female patients vs. female controls, and male patients vs. male controls. Predictive models were used to explore the role of gut microbiota in predicting TC. Correlations between gut microbiota and T stage (i.e., T1 to Tx) were also investigated. The alpha and beta diversities differed between the patients and healthy participants. Sex-specific analysis demonstrated that Blautia and Alistipes were the dominant bacteria shared by both female and male patients. A 25.0% overlap in dominant bacteria was found between the male and female patients. The unique dominant bacteria in female patients constituted 43.8% (7/16) and mainly included Schaalia, Moraxella and Alicyclobacillus. In male patients, the unique dominant bacteria constituted 55.6% (10/18) and included Holdemanella, Clostridium_sensu_stricto, and Senegalimassilia. Regardless of sex, Catenibacterium was the distinguishing feature between patients and healthy participants (area under the curve [AUC] = 0.911). When combined with Aquabacterium and Dialister, the predictive accuracy increased (AUC = 0.992). Male and female patients exhibited both shared and distinct sex-specific microbiota compositions, potentially influenced by hormonal regulation, immune responses, and metabolic differences. These variations may contribute to differences in TC susceptibility and progression. The findings underscore the need for further research to confirm the functional significance of the identified microbiota and explore their potential clinical applications.