title: Impact of demographics on human gut microbial diversity in a US Midwest population.
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 R(2) 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.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Health Sciences Research, Mayo Clinic , Rochester, Minnesota , United States.
authors.forename: Euijung
authors.initials: E
authors.lastname: Ryu
authors.affiliation: Department of Health Sciences Research, Mayo Clinic , Rochester, Minnesota , United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hathcock
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States; Division of Biostatistics and Epidemiology, Weill Medical College of Cornell University, New York, New York, United States.
authors.forename: Karla
authors.initials: K
authors.lastname: Ballman
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States; Department of Surgery, Mayo Clinic, Rochester, Minnesota, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chia
authors.affiliation: Department of Health Sciences Research, Mayo Clinic , Rochester, Minnesota , United States.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.affiliation: Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States; Department of Surgery, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Nelson
keywords: Demographics; Effect size; Microbial diversity; Microbiome; Target population
references.citation: Gut. 2001 Feb;48(2):198-205
references.pmid: 11156640
references.citation: Curr Opin Clin Nutr Metab Care. 2003 Jan;6(1):49-54
references.pmid: 12496680
references.citation: Gastroenterology. 2004 May;126(6):1620-33
references.pmid: 15168372
references.citation: Appl Environ Microbiol. 2005 Dec;71(12):8228-35
references.pmid: 16332807
references.citation: Nature. 2006 Dec 21;444(7122):1022-3
references.pmid: 17183309
references.citation: Nature. 2006 Dec 21;444(7122):1027-31
references.pmid: 17183312
references.citation: Nature. 2009 Jan 22;457(7228):480-4
references.pmid: 19043404
references.citation: Nat Rev Immunol. 2009 May;9(5):313-23
references.pmid: 19343057
references.citation: Curr Pharm Des. 2009;15(13):1546-58
references.pmid: 19442172
references.citation: Br J Nutr. 2010 Jan;103(2):227-34
references.pmid: 19703328
references.citation: Nature. 2010 Mar 4;464(7285):59-65
references.pmid: 20203603
references.citation: Nat Rev Genet. 2010 Oct;11(10):733-9
references.pmid: 20838408
references.citation: Nature. 2011 May 12;473(7346):174-80
references.pmid: 21508958
references.citation: ISME J. 2012 Aug;6(8):1621-4
references.pmid: 22402401
references.citation: Nat Rev Genet. 2012 Mar 13;13(4):260-70
references.pmid: 22411464
references.citation: Nature. 2012 Jun 13;486(7402):207-14
references.pmid: 22699609
references.citation: Bioinformatics. 2012 Aug 15;28(16):2106-13
references.pmid: 22711789
references.citation: PLoS One. 2012;7(6):e34242
references.pmid: 22719824
references.citation: PLoS Biol. 2012;10(8):e1001377
references.pmid: 22904687
references.citation: Nature. 2012 Oct 4;490(7418):55-60
references.pmid: 23023125
references.citation: Am J Epidemiol. 2013 Feb 1;177(3):197-201
references.pmid: 23296358
references.citation: PLoS One. 2013;8(3):e59260
references.pmid: 23516617
references.citation: Obesity (Silver Spring). 2013 Dec;21(12):E607-15
references.pmid: 23526699
references.citation: PLoS One. 2013 Aug 06;8(8):e70803
references.pmid: 23940645
references.citation: Cell Host Microbe. 2013 Aug 14;14(2):195-206
references.pmid: 23954158
references.citation: Mayo Clin Proc. 2013 Sep;88(9):952-62
references.pmid: 24001487
references.citation: PLoS One. 2013 Aug 27;8(8):e71108
references.pmid: 24013136
references.citation: Elife. 2013 Nov 05;2:e01202
references.pmid: 24192039
references.citation: J Hepatol. 2014 May;60(5):940-7
references.pmid: 24374295
references.citation: Gastroenterology. 2014 May;146(6):1534-1546.e3
references.pmid: 24406471
references.citation: PLoS Pathog. 2014 Feb 20;10(2):e1003829
references.pmid: 24586144
references.citation: MBio. 2014 May 06;5(3):e01021-14
references.pmid: 24803517
references.citation: Microb Ecol Health Dis. 2014 Jun 03;25:null
references.pmid: 24936169
references.citation: FEBS Lett. 2014 Nov 17;588(22):4223-33
references.pmid: 25307765
references.citation: Cell. 2014 Nov 6;159(4):789-99
references.pmid: 25417156
references.citation: PLoS One. 2014 Dec 15;9(12):e114804
references.pmid: 25506826
references.citation: Genome Biol. 2014 Dec 03;15(12):531
references.pmid: 25517225
references.citation: ISME J. 2015 Sep;9(9):1979-90
references.pmid: 25647347
references.citation: PeerJ. 2016 Feb 01;4:e1634
references.pmid: 26855872