Accounting for reciprocal host–microbiome interactions in experimental science

• Published in: Nature (London) 2016-06, Vol.534 (7606), p.191-199
• Main Authors: Stappenbeck, Thaddeus S., Virgin, Herbert W.
• Format: Article
• Language: English
• Subjects: 631/1647/767; 64/60; 692/308/1426; Animals; Biology; Biomedical Research - methods; Biomedical Research - standards; Chromosomes; Experimental design; Experiments; Fecal Microbiota Transplantation; Female; Gene expression; Genomes; Humanities and Social Sciences; Humans; Male; Mammals; Metagenome - genetics; Mice; Microbiota (Symbiotic organisms); Microbiota - genetics; Microorganisms; Models, Animal; multidisciplinary; perspective; Phenotype; Physiological research; Physiology; Reference Standards; Reproducibility of Results; Research Design; Science; Sequence Analysis, DNA
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature18285

Mammals are defined by their metagenome, a combination of host and microbiome genes. This knowledge presents opportunities to further basic biology with translation to human diseases. However, the now-documented influence of the metagenome on experimental results and the reproducibility of in vivo mammalian models present new challenges. Here we provide the scientific basis for calling on all investigators, editors and funding agencies to embrace changes that will enhance reproducible and interpretable experiments by accounting for metagenomic effects. Implementation of new reporting and experimental design principles will improve experimental work, speed discovery and translation, and properly use substantial investments in biomedical research. This work highlights the critical challenges in experimental design and interpretation due to important combinatorial effects of host and microbial genes, and calls for the development of minimal reporting requirements to improve the interpretation and reproducibility of experimental biology. Experimental design and the microbiome Recent studies have indicated that differences in mammalian genetics explain only a fraction of observed phenotypic variation. The microbiome — principally its bacterial, viral and fungal components — is also of great importance in determining physiological responses. In this Perspective, Thaddeus Stappenbeck and Herbert Virgin highlight the need for experimental design and interpretation that takes account of the interactions between host and microbiome genes, focusing on the workhorse of genetic and medical research, the laboratory mouse.