Unravelling the effects of the environment and host genotype on the gut microbiome

• Published in: Nature reviews. Microbiology Vol. 9; no. 4; pp. 279 - 290
• Main Authors: Spor, Aymé, Koren, Omry, Ley, Ruth
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2011; Nature Publishing Group
• Subjects: 41; 631/208/727; 692/698/2741/2135; Adaptive Immunity - genetics; Animals; Bacteria; Biomedical and Life Sciences; Chronic diseases; Chronic illnesses; Diabetes; Diet; Disease; Environment; Environmental aspects; Environmental effects; Gastrointestinal Tract - immunology; Gastrointestinal Tract - microbiology; Genes; Genetic aspects; Genetics; Genotype; Humans; Immunity, Innate - genetics; Infectious Diseases; Inflammatory bowel disease; Life Sciences; Medical Microbiology; Metagenome - immunology; Metagenome - physiology; Mice; Mice, Inbred Strains; Microbial Consortia - immunology; Microbial Consortia - physiology; Microbiology; Microbiota; Microbiota (Symbiotic organisms); Parasitology; Penis; Physiological aspects; Population structure; Quantitative genetics; review-article; Risk factors; Twin studies; Twins; Vagina; Virology; United States
• ISSN: 1740-1526; 1740-1534; 1740-1534
• DOI: 10.1038/nrmicro2540

Key Points The gut microbiota can positively and negatively affect host health, and the specific composition of the microbiota may be important for host health and fitness. Environment factors (diet, host environment, maternal effect, stochasticity, and so on) interact to shape the gut microbiota, but how they interact with host genetics to influence the composition of the microbiota is not well understood. A recent quantitative trait loci (QTL) study highlighted host genetic factors that control the composition of the gut microbial community. Candidate gene approaches (that monitor genetic diversity at a given locus in humans and the effects of gene insertions or deletions in mice) implicate host genomic loci in shaping gut microbial diversity. Host genes that have been identified as important for determining microbial diversity in the gut have roles primarily in the innate and adaptive immune system, and in metabolism. Genome-wide association studies can consider the gut microbiota as a host phenotypic trait, but can also incorporate the microbiota into studies of host gene–environment interactions in the context of chronic inflammatory disease. In recent years, the composition of the gut microbiome has become the subject of intensive study. In this Review, Spor, Koren and Ley describe how host genetics and the environment shape the gut microbiome, both in health and in chronic disease. To what extent do host genetics control the composition of the gut microbiome? Studies comparing the gut microbiota in human twins and across inbred mouse lines have yielded inconsistent answers to this question. However, candidate gene approaches, in which one gene is deleted or added to a model host organism, show that a single host gene can have a tremendous effect on the diversity and population structure of the gut microbiota. Now, quantitative genetics is emerging as a highly promising approach that can be used to better understand the overall architecture of host genetic influence on the microbiota, and to discover additional host genes controlling microbial diversity in the gut. In this Review, we describe how host genetics and the environment shape the microbiota, and how these three factors may interact in the context of chronic disease.