Hydrogen Breath Test Dynamics Reflect Intestinal Fermentation Rather than Systemic Inflammation: A Data-Driven...

Background: Hydrogen breath testing is commonly used to assess intestinal fermentation and diagnose small intestinal bacterial overgrowth (SIBO). However, it remains unclear whether hydrogen production reflects systemic inflammatory or metabolic status. This study evaluated the relationship between hydrogen production dynamics and systemic biomarkers using a data-driven analytical approach. Methods: This cross-sectional study included 162 adults undergoing lactulose hydrogen breath testing. Hydrogen production was characterized using continuous measures, including area under the curve (AUC), early and late hydrogen responses, and unsupervised clustering-derived hydrogen response groups. Associations with serum 25-hydroxyvitamin D, C-reactive protein (CRP), leukocyte count, and interleukin-6 (IL-6) were assessed using multivariable regression models adjusted for age and body mass index (BMI). Results: Hydrogen production showed substantial interindividual variability. Unsupervised analysis identified low-, intermediate-, and high-hydrogen response groups. Differences between groups were driven mainly by overall fermentation intensity rather than distinct temporal response profiles. No significant associations were observed between hydrogen production metrics and systemic biomarkers. Hydrogen-related variables were not independently associated with vitamin D, CRP, leukocyte count, or IL-6 concentrations. In contrast, BMI was consistently associated with inflammatory markers, particularly CRP and IL-6. Correlation analyses demonstrated strong relationships among hydrogen-derived variables but weak associations with systemic parameters. Conclusions: Data-driven analysis revealed marked heterogeneity in intestinal hydrogen production but no detectable association with systemic inflammatory or metabolic markers within the present cohort. These findings suggest that hydrogen breath test metrics primarily reflect local intestinal fermentation rather than systemic physiological status. Hydrogen breath testing remains useful for assessing gastrointestinal function, but no evidence supporting its value as a marker of systemic inflammation was identified in the present cohort.