Longitudinal interactions between levels of serum cytokine and the microbiome from four body sites

Abstract The human body is co-habituated with trillions of microbes, which are actively interacting with the human immune system. Our previous study demonstrated that a subset of individuals, characterized by a chronic absence of serum Interleukin (IL)-17 and IL-22, is more likely to be resistant to insulin compared with individuals with detectable serum IL-17/IL-22. Additional analysis pointed out that such an absence of IL-17 and IL-22 is associated with the low abundance of the gut microbiome that belongs to the class of Clostridia. To better understand the interactions between serum cytokines and microbiome, we curated a dataset from the iHMP that contains 86 individuals with a study duration from 5 months to 6 years, whose microbiome has been characterized from four body sites include: stool (n=927), skin (n=1128), nasal (922), oral (n=1001). Their serum cytokines had been characterized using 62-plex Luminex antibody-conjugated bead capture assay. The longitudinal interaction between microbiome abundance and serum cytokine are modeled by Bayesian Mixed-Effects Model, and the interaction between microbiome richness and serum cytokine are modeled by Linear Mixed Models. We found the interactions are strongest in the gut compared to the other three body sites, but it is highly territory specific. For example, Moraxella from the skin is negatively correlated with multiple cytokines, but not Moraxella from the nasal. Among all cytokines, IL-1 signaling is the strongest modulator of microbiome abundance in all four body sites, but LEPTIN and GMCFS are more potent when focused on richness. Our results indicate that the immune regulation of the microbiome is active on multiple body sites, and such interaction is genera and cytokine specific. This work was supported by the National Institutes of Health Common Fund Human Microbiome Project (HMP) (1U54DE02378901). Dr. Xin Zhou received support from the Stanford Aging and Ethnogeriatrics (SAGE) Research Center under NIH/NIA grant P30AG059307. The SAGE Center is part of the Resource Centers for Minority Aging Research (RCMAR) Program led by the National Institute on Aging (NIA) at the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and does not necessarily represent the official views of the NIA or the NIH.