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  • Review Article
  • Published:

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

Nature Reviews Microbiology volume 9, pages 279–290 (2011)Cite this article

Subjects

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.

Abstract

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.

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Figure 1: Microbial community composition at different body locations in a healthy human.
Figure 2: Gut microbial dysbiosis associated with disease.
Figure 3: Host genetic variants, their effects on the composition of the gut microbiota, and the corresponding host disease state.

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Acknowledgements

We thank A. Benson, D. Pomp, L. Angenent and the three reviewers for helpful comments on the manuscript, and J. Koenig for early discussions. We are grateful for a Beckman Young Investigator Award, and to The Hartwell Foundation, the David and Lucile Packard Foundation, the US National Science Foundation (IOS-0958,184), and the US National Institutes of Health Human Microbiome Project Data Analysis and Coordination Center (U01 HG004866) for support.

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  1. Aymé Spor and Omry Koren: These authors contributed equally to this article.

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  1. Department of Microbiology, Cornell University, Ithaca, New York, 14853, USA

    Aymé Spor, Omry Koren & Ruth Ley

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  1. Aymé Spor
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Correspondence to Ruth Ley.

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Glossary

Microbiota

A microbial community or assemblage.

Dysbiosis

A shift in the relative abundances of the microbial taxa compared with the adundances that are observed in healthy animals.

Microbiome

The complete set of genes within a microbiota.

Germ-free

Pertaining to an animal: lacking a microbiome; born and raised under sterile conditions for research purposes.

Adiposity

The property of containing fat.

β-diversity

A measure of diversity that describes the differences between any two ecosystems (for example, the UniFrac distance metric). Related to α-diversity and γ-diversity, which are measures of the diversity in a single ecosystem and across a group of ecosystems, respectively.

UniFrac

A β-diversity measure that is phylogeny based. Microbial communities are more similar if they are composed of members that are more closely related, phylogenetically, as this implies a shared evolutionary past. UniFrac units range from 0 (identical communities) to 1 (totally different communities).

Altered Schaedler flora

A standard enteric flora containing eight species that are known to exhibit tissue tropism, occupying different niches in the mouse gastrointestinal tract.

Quantitative trait locus

A genomic region for which variation is associated with the quantitative variation in a phenotypic trait.

Heritability

The proportion of phenotypic variation in a population that is attributable to genetic variation among individuals.

Fingerprinting-based comparison

A molecular technique for the study of nucleic acids using either denaturing-gradient gel electrophoresis (DGGE) or temporal temperature gradient gel electrophoresis (TTGE). Another method is terminal restriction fragment length polymorphism (T-RFLP), in which the DNA is amplified using fluorescence-labelled primers, digested using restriction enzymes and then detected. In microbial ecology, these techniques are used to compare microbial communities.

Dam

A female animal parent.

Advanced intercross line

An experimental mouse population used for the study of quantitative trait loci (QTL). This population is created by randomly intercrossing strains and then intercrossing the mice in subsequent generations until the desired number of generations is achieved. This results in mice with many recombinations in the genome, which is required for QTL studies.

Genome-wide association study

A genetic approach aiming to relate genome-wide variation in genetic markers to variation in any given phenotype. The microbiota, or its components, can be considered as a host phenotype.

ob/ob mouse

A mouse carrying two copies of a non-functional leptin gene (Ob; also known as Lep). These mice are leptin deficient and obese.

Zucker rat

A rat that is deficient in the leptin receptor (FA; also known as LEPR and OBR) and is obese.

Hyperphagia

Over-consumption of food.

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Spor, A., Koren, O. & Ley, R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol 9, 279–290 (2011). https://doi.org/10.1038/nrmicro2540

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