Microbiota-supportive diets and hyperlipidemia: The mediating role of systemic inflammation

Hyperlipidemia is a major modifiable risk factor for cardiovascular disease, and emerging evidence suggests a critical role of the gut microbiota in lipid metabolism. The Dietary Index for Gut Microbiota (DI-GM) is a novel tool designed to capture the microbiota-supportive potential of habitual dietary patterns, yet its association with lipid abnormalities remains underexplored in large populations.

We analyzed data from 21,352 adults in the 2010-2020 cycles of the National Health and Nutrition Examination Survey (NHANES). The DI-GM, reflecting 14 microbiota-relevant dietary components, was derived from 24-hour recall data. Hyperlipidemia was defined using standard lipid thresholds or lipid-lowering medication use. Survey-weighted logistic regression, restricted cubic spline analysis, and mediation analysis using the systemic immune-inflammation index (SII) were performed to assess associations and potential mechanisms.

Higher DI-GM scores were significantly associated with lower odds of hyperlipidemia (fully adjusted OR for highest vs. lowest category = 0.806; 95% CI: 0.735-0.883). A dose-response relationship was confirmed in spline models. Mediation analysis showed that systemic inflammation, as quantified by SII, accounted for 17.8% of the observed association, suggesting an immunometabolic pathway linking diet and lipid status.

Microbiota-oriented dietary patterns, as captured by the DI-GM, are inversely associated with hyperlipidemia in U.S. adults. These findings highlight the value of integrating microbiome-relevant dietary assessment into lipid management strategies. Partial mediation by systemic inflammation underscores a potential mechanistic link warranting further investigation through longitudinal and interventional studies.