Integrated Inflammatory Biomarker Profiling Differentiates Degrees of Body Mass Index Beyond Intestinal...

Obesity is characterized by low-grade systemic inflammation and alterations in gut-related immune pathways that may contribute to metabolic dysfunction. Composite biomarker indices may better capture these complex processes than individual markers, although their performance may differ across biological domains. In this cross-sectional study, 88 adults without diabetes or infection were categorized as BMI < 25 kg/m² (n = 20), BMI 25-29.9 kg/m² (n = 34), or BMI ≥ 30 kg/m² (n = 34). Circulating biomarkers reflecting systemic inflammation (high-sensitivity C-reactive protein, ferritin, interleukin-6, presepsin) and intestinal barrier-related activity (β-defensin-2, regenerating islet-derived protein 3 alpha) were measured and subsequently combined into two composite indices: the Inflammatory Load Index, derived from inflammatory markers, and the Barrier Activation Index, derived from barrier-related markers. Group differences were assessed using analysis of variance with post hoc testing. Additional analyses included effect size estimation, receiver operating characteristic (ROC) analysis, and logistic regression. Individual biomarkers showed limited differences across BMI categories. The Inflammatory Load Index differed significantly across BMI categories (p = 0.040), with higher values observed in individuals with BMI ≥ 30 kg/m² compared with those with BMI 25-29.9 kg/m² (p = 0.032; Cohen's d = 0.80), while the Barrier Activation Index did not differ (p = 0.257). In ROC analysis, the Inflammatory Load Index discriminated BMI ≥ 30 kg/m² with an area under the curve of 0.720 (95% confidence interval 0.576-0.851), yielding 77.8% sensitivity and 67.7% specificity. Each one standard deviation increase in the index was associated with higher odds of obesity (odds ratio 2.34, 95% confidence interval 1.22-4.49; p = 0.011). In conclusion, a composite inflammatory biomarker index, but not a barrier-related index, differentiates degrees of BMI in individuals without diabetes. These findings support integrated biomarker approaches for reflecting obesity-related biological burden beyond single markers. However, these observations are based on cross-sectional data and do not imply causality.