Possible association of serum trimethylamine N-oxide and INSL3 levels with the gut–testis axis in cryptorchidism

Abstract Cryptorchidism, a common congenital condition in male children, has been associated with impaired testicular function and increased risk of infertility. Recent evidence suggests that gut microbiota-derived metabolites, such as trimethylamine N-oxide (TMAO), may influence reproductive health via systemic inflammation and oxidative stress. This study aimed to investigate serum levels of TMAO, insulin-like 3 factor (INSL3), and human chorionic gonadotropin (hCG) in patients with undescended testes. Serum TMAO was quantified by LC-MS/MS and INSL3 and hCG by ELISA in 30 patients and 30 healthy age-matched controls. Results showed significantly elevated TMAO and reduced INSL3 levels in the patient group ( p < 0.01 and p = 0.025, respectively), whereas hCG levels showed no significant difference. These findings support the hypothesis that metabolic and hormonal alterations may play a role in the pathophysiology of cryptorchidism. TMAO may reflect systemic dysbiosis or inflammation potentially associated with impaired testicular function. Further studies are warranted to explore the gut–testis axis and asses the potential clinical relevance of TMAO and INSL3 as biomarkers in male reproductive health.