Abstract
The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial β-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial α-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R2 values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies.
Highlights
Humans are populated by a vast number of microbes
Gut microbiota profile of the Midwestern United States As revealed by a comparison with Behavioral Risk Factor Surveillance Survey (BRFSS) data, the distribution of important demographic variables within the Midwestern Reference Panel (MWRP) cohort, which consists of 118 subjects drawn from the Mayo Clinic Biobank, generally reflects the demographic characteristics of the Midwestern United States, alcohol users are slightly over-represented in subjects older than 50 years of age (Table 1)
An average of 402 operational taxonomic unit (OTU) was detected in each subject
Summary
It is estimated that bacterial cells associated with the human body outnumber human cells by a factor of 10 (Cho & Blaser, 2012) These microbes and their genetic content constitute the human. The gut microbiome alone accounts for more than three million genes, more than 100 times the number of human genes (Qin et al, 2010). The microbiome has both digestive and metabolic functions (Cani & Delzenne, 2009) and plays an important role in the development of the host immune system (Round & Mazmanian, 2009). Extensive evidence shows that a core microbiome is responsible for maintaining a healthy state; any significant deviation may affect an individual’s risk of disease (Sartor, 2004; Ley et al, 2006; Huse et al, 2012; Human Microbiome Project Consortium, 2012; Zhang et al, 2015)
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