KU Leuven – University of Leuven, Department of Microbiology and Immunology, Rega Institute, Herestraat 49, B-3000 Leuven, Belgium; VIB, Center for Microbiology, Kasteelpark Arenberg 31, B-3000 Leuven, Belgium; Research Group of Microbiology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium
For the benefit of future clinical studies, it is critical to establish what constitutes a “normal” gut microbiome, if it exists at all. Using 16S RNA gene based gut microbiome profiling we analyzed more than 1200 fecal samples of an average population cohort in Belgium. Building upon rich metadata and a two-cohort design, we identified a set of microbiota covariates with a replication rate of over 92% and a cumulative, non-redundant effect size of 7.63%. This suggests the influence of additional, currently unknown covariates as well as intrinsic microbial ecological processes. We showed that some of the medical conditions targeted by fecal microbiota research have much smaller microbiome effect sizes than commonly assumed. However, some of the covariates that we identified (such as stool consistency and medication) are currently largely ignored and should be taken into account in future clinical studies. Our power analyses showed that large-scale study design is indispensable for characterizing microbiome shifts, even in a controlled setting. Yet, in order to take gut microbiota research to the next level, up-scaling is not enough and should be combined with the integration of quantitative microbiome profiling techniques. First analyses using such approaches shed a whole different light on the gut microbiota in health and disease. We think these insights and new methodologies will pave the way for the development of microbiome research as a clinical and diagnostic field.