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Abstract

Objective: Trimethylamine N-oxide (TMAO), a metabolite derived from gut microbiota, has been linked to various chronic inflammatory conditions. However, its potential role in acute inflammation, such as pediatric acute appendicitis, remains unclear. This exploratory diagnostic study aimed to assess the preliminary diagnostic performance of serum and urinary TMAO levels in differentiating appendicitis subtypes. Methods: In this prospective study, 137 pediatric patients who underwent surgery for suspected acute appendicitis were included. Based on histopathological findings, patients were categorized into negative, non-complicated, and complicated appendicitis groups. Serum and urinary TMAO levels were measured using liquid chromatography–tandem mass spectrometry. Group comparisons were performed using appropriate parametric and non-parametric tests. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression models were constructed to identify independent predictors of complicated appendicitis. Results: Urinary TMAO levels were mildly elevated in patients with non-complicated appendicitis compared to both negative and complicated cases, representing a statistically significant but modest difference (median [Q1–Q3]: 30,100 [11,500–58,220.9] ng/mL vs. 22,500 [6,537.46–34,563.2] ng/mL,p = 0.046). In contrast, serum TMAO levels did not differ significantly among the study groups (p = 0.292). ROC analysis demonstrated modest discriminatory performance of urinary TMAO in differentiating complicated from non-complicated appendicitis, whereas serum TMAO showed no diagnostic utility. In multivariable logistic regression analyses, C-reactive protein emerged as the only independent predictor of complicated appendicitis, while neither serum nor urinary TMAO was independently associated with disease severity. Conclusion: Urinary TMAO levels may reflect early-stage metabolic or microbiota-related alterations in pediatric acute appendicitis but demonstrate limited discriminatory power when used in isolation. These findings suggest that urinary TMAO should be considered a hypothesis-generating, adjunctive metabolic marker rather than a standalone diagnostic tool. Further multicenter studies incorporating dietary, microbiota, and renal function assessments are warranted to clarify its clinical relevance.

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