The gut microbiome as mediator between diet and its impact on immune function

Abstract

Dietary habits may affect inflammatory status in humans. Here we explore this interaction as well as the potential mediating role of the gut microbiome (GM), given that the GM is both involved in processing of dietary components and influences the immune system. A cross-sectional analysis of a sample of 482 healthy participants (207 males and 275 females) was performed. Dietary intake was assessed by a semiquantitative food questionnaire. Adipokines and soluble inflammatory mediators were assayed with multiple immunoassays and ELISA. Microbial DNA was extracted from frozen stool samples of 471 participants. Polychoric correlation analysis was used to establish dietary patterns, and joint multivariate associations between these dietary patterns and immune biomarkers were studied using regression analyses with adjustment for sex, age, BMI, smoking, education levels and physical exercise and other dietary patterns. Non-parametric entropy mediation was applied to investigate whether diet-immune relationships are mediated by abundance of microbial species. In this cohort, we identified three dietary patterns, characterized as "high-meat" (meat and sweetened drink), "prudent diet" (fish, fruit, legumes and vegetables) and "high alcohol" (higher alcohol consumption). Higher adherence to prudent diet was associated with a higher adiponectin level. The high alcohol pattern was associated with high concentrations of circulating concentrations of pro-inflammatory markers (CRP, IL-6, VEGF). Dialister invisus was found to mediate the relationship between a prudent dietary pattern and adiponectin, AAT, CRP, IL-6, and VEGF. In conclusion, a meat-based diet and a diet with high alcohol consumption were associated with high concentrations of biomarkers of chronic low-grade inflammation, and conversely, a prudent diet was associated with anti-inflammatory biomarkers. Diet-inflammation regulation may differ between sexes. Mediation analyses revealed that the association between prudent diet and immune function was partially mediated by the GM. The study adds to our understanding of the associations between diet, the immune system and the GM in a healthy population.

Figure 1

Dietary patterns derived by polychoric correlation analysis. (A) Factor loadings for the 10 food groups used in the extraction of the most common dietary patterns among all subjects (n = 482). In high-meat pattern, meat consumption has the highest loading (0.754); In prudent diet pattern, the top four loadings were vegetables (0.575), legumes (0.519), fruit (0.220) and fish (0.209); In high-alcohol consumption, daily (0.522) and weekend (0.503) alcohol consumption weighted the highest. Factor loadings were derived by polychoric correlation with varimax rotation. (B) Correlation matrix shows paired correlations of all food items with hierarchical clustering. Red color indicates positive correlations and blue color indicates negative correlations. (C) Boxplots show the differences of scores of three dietary patterns between men and women by Wilcoxon test, ***: P < 0.001.

Figure 2

Association between scores of dietary patterns and cytokines concentration. (A) The P values (FDR corrected per column) of the regression between each dietary pattern and circulating inflammatory cytokines by log transformation. Red in figure legend indicates an FDR with positive correlation and blue indicates FDR with negative correlation. (B) Scatterplots show the effect of dietary pattern on cytokines with significant correlation. Blue dots and lines indicate males, red dots and lines indicate females.

Figure 3

Results of the NPEM method depicted in the mediation framework. (A) Dialister invisus mediates the relationship between the prudent diet and diponectin, AAT, CRP, IL-6 and VEGF (P = 0.041). The alpha, beta and gamma pathways represents the effect of the prudent diet on Dialister invisus, the effect of Dialister invisus on the immune factors, and the effect of the prudent diet on the immune factors, respectively. FDR corrected p-values of the pathways are shown for each immune factor. IF: information score. (B) Scatterplots show the relationship between prudent diet on D.invisus and D.invisus on immune markers, the unit is 1 out of 100.

Figure 4

Representation of a mediation model with an exposure (X), mediator (M) and response (Y) and their relationships (α, β, γ).