Population-level analysis of gut microbiome variation
Gwen Falony, Marie Joossens, Sara Vieira‐Silva, Jun Wang, Youssef Darzi, Karoline Faust, Alexander Kurilshikov, Marc Jan Bonder, Mireia Valles‐Colomer, Doris Vandeputte, Raúl Y. Tito, Samuel Chaffron, Leen Rymenans, Chloë Verspecht, Lise De Sutter, Gipsi Lima‐Mendez, Kevin D’hoe, Karl Jonckheere, D Homola, Roberto García, Ettje F. Tigchelaar, Linda Eeckhaudt, Jingyuan Fu, Liesbet Henckaerts, Alexandra Zhernakova, Cisca Wijmenga, Jeroen Raes
Abstract
Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.