Correlation-based network analysis for biomarkers in obesity

Background: Obesity is associated with chronic activation of the immune system and an altered gut microbiome, leading to increased risk of chronic disease development. As yet, no biomarkers have been found to distinguish individuals at greater risk of obesity-related disease. The aim of this study was to explore a correlation-based network approach to find existing patterns of immune-microbiome interactions in obesity.Results: The current study performed correlation-based network analysis on five different datasets obtained from 11 obese and 12 healthy weight men: anthropometric measures, metabolic measures, immune cell abundance, serum cytokine concentration, and gut microbial composition. The obese cohort had a denser network (total number of edges, n=237) compared to the healthy network (n= 190). Within the obese network, immune cell abundance was found to be correlated to biomarkers from all four other datasets while in the healthy network, immune cell abundance was only correlated with serum cytokine concentration and gut microbial composition. Neutrophils within the obese immune cell abundance group were correlated with the most number of other biomarkers. Two different types of neutrophil measurements were taken, an abundance measure from immune cell gene expression and a whole blood count, with correlations to 10 and 6 other biomarkers, respectively. From the combined number of 16 biomarkers, 4 biomarkers were correlated between the two measurements: Anaerostipes abundance, Blautia abundance, EscherichialShigella abundance and Flavonifractor abundance.Conclusion: The obesity-related dysregulation of immune biomarkers was suggested by the high connectivity of immune cells in the obese network compared to the healthy network. Our study also revealed the importance of integrated analysis to uncover immune-microbiome interactions in obesity that are likely to have been missed in univariate analysis.