The CHRIS Salivary Microbiome - Characterization of the salivary microbiome in a large sample of South Tyrolean adults in relation to lifestyle, environment, and genetics

The oral microbiome is a key component of the human body and has been associated with several habits and diseases. Despite its important role in health, it remains relatively understudied, compared to the gut microbiome. To deepen our understanding of the oral microbiome and its links to host conditions, the main aim of my PhD thesis was to characterize the lifestyle, environmental and genetic determinants of the salivary microbiome using data from CHRISMB, a convenience sample within the Cooperative Health Research in South Tyrol (CHRIS) study. With more than 1,900 samples, CHRISMB is one of the largest salivary microbiome data resources in the world. First, I studied the association between the salivary microbiome and smoking status and degree of exposure both from the compositional and predicted metabolism perspective. I found associations with 44 genera, 11 of which were also proportionally affected by the degree of exposure to tobacco. Intriguingly, these associations highlight a novel role of salivary microbiome metabolism in cardiovascular diseases through periodontium degeneration via the nitrate reduction and extracellular matrix degradation pathways. My second contribution focused on the role of geography, family relatedness, and genetics in shaping CHRISMB diversity. I investigated the associations between household, municipality and altitude of residence, heritability, and genetic marker associations (mbGWAS). I confirmed that cohabitation is a strong driver of microbiome similarity, while municipality and altitude of residence did not show strong associations. Siblings living apart had a more similar microbiota than unrelated and non-cohabiting individuals. Sixteen out of 142 taxa had a significant heritability component, while 34 had a significant household component. A mbGWAS Gene-level analysis resulted in one association between rare variants in the SRFBP1 and LOX genes locus and Selenomonas noxia. This work confirmed that host genetics and familial relationships has a modest but significant association with the salivary microbiome composition and that the environment and lifestyle are strongly associated. In summary, this thesis deepens our understanding of population-level factors associated with salivary microbiome variability, which can help design future hypothesis driven studies.