Gut Microbiota‐Modulating Diets Attenuate Cardiovascular‐Kidney‐Metabolic Syndrome via Inflammatory Mediation: Insights From NHANES and Machine Learning Model

The role of gut microbiota-modulating diets in cardiovascular-kidney-metabolic (CKM) syndrome progression is poorly understood. This study investigated associations between the dietary index for gut microbiota (DI-GM) and advanced CKM risk, with a focus on inflammatory mediation. Cross-sectional data from 12,068 NHANES participants (2007-2020) were analyzed. Advanced CKM stages (3-4) were classified using American Heart Association (AHA) criteria. DI-GM scores were derived from 14 dietary components, and inflammatory biomarkers (e.g., dietary inflammatory index [DII], neutrophil to lymphocyte ratio [NLR], systemic inflammation response index [SIRI]) were assessed. Multivariable logistic regression, mediation analysis, and machine learning (XGBoost, SHAP) evaluated associations and predictive performance. High DI-GM adherence (≥6) was associated with a 25% reduction in advanced CKM risk, while each unit increase was associated with a 7% lower risk. Inflammatory biomarkers mediated 42.88% (DII) to 5.59% (neutrophils) of this association. XGBoost identified coffee, refined grains, and fat as top risk predictors. This cross-sectional study underscores the protective role of DI-GM against CKM progression, mediated substantially by inflammation suppression. While these results highlight promising associations, the cross-sectional design necessitates caution in inferring causality. Machine learning underscores the importance of dietary synergy over isolated components, advocating for integrated dietary-microbiota interventions in precision CKM management. PRACTICAL APPLICATIONS: What is currently known about this topic? Cardiovascular-kidney-metabolic (CKM) syndrome, formally defined in 2023, affects over 25% of US adults, yet evidence linking gut microbiota-targeted dietary patterns to advanced CKM risk remains limited. What is the key research question? Higher dietary index for gut microbiota (DI-GM) scores-characterized by fiber-rich, fermented, and plant-based components-are inversely associated with advanced CKM risk, particularly in males sedentary and hypertension subgroups. How might this study influence clinical practice? Inflammatory biomarkers mediate 42.88% of the association between DI-GM and CKM progression, with machine learning identifying coffee, refined grains, and dietary fat as key contributors to risk stratification, supporting microbiota-driven precision nutrition strategies.