Associations between gut microbiome and circulating cytokines: a cross-sectional analysis in the FINRISK 2002 population cohort

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Background A growing body of evidence suggests a relationship between gut microbiome and circulatingcytokines, yet there is still a lack of large-scale population-based studies investigating gut microbiome-cytokineassociations. In this cross-sectional study, we aimed at investigating the associations of gut microbiome (exposurevariable) with 45 cytokines and C-reactive protein (CRP) (outcome variables) in the population-based FINRISK 2002cohort (N = 2,398). Our analyses focused mainly on gut microbiome alpha diversity, beta diversity, differentiallyabundant taxa, and predicted functions. All statistical models were adjusted for age, sex, BMI, diabetes, and smoking.Results Using linear modeling, we identified an inverse association of the gut microbial alpha diversity (Shannonindex) with CRP (β=-0.062 ± 0.019/standard deviation (SD), False Discovery Rate adjusted p-value (FDR-P) = 0.025),interleukin-8 (IL-8) (β=-0.066 ± 0.021/SD, FDR-P = 0.025), and interferon-γ-inducible protein 10 (IP-10) (β=-0.063 ± 0.02/SD, FDR-P = 0.025). For beta diversity, linear modeling revealed that the first axis of Principal Component Analysis(PCA) describing the most strongly varying parts of the microbial community composition across population wasinversely associated with CRP (β=-0.071 ± 0.019/SD, FDR-P = 0.008) and the second axis was inversely associatedwith macrophage inflammatory protein-1β (MIP-1B) (β=-0.082 ± 0.021/SD, FDR-P = 0.008), and monokine inducedby interferon-γ (MIG) (β=-0.071 ± 0.019/SD, FDR-P = 0.008). The majority of the top taxa contributing to the first andsecond PCA axes belonged to class Bacilli (7/10) and class Gammaproteobacteria (9/10), respectively. In addition tothis, we detected 8 significant associations of specific gut microbiome taxa (species-level) with cytokines and CRPusing linear models. The majority of significant taxa belonged to class Clostridia_258483 (5/8) and class Bacteroidia(2/8). We did not detect any significant associations between species-specific predicted MetaCyc pathways (using allprevalent pathways) and cytokines or CRP. When analysis was limited to pathways associated with significant speciesonly, we observed a positive association between purine synthesis predicted pathways in B. thetaiotaomicron and CRP.

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