Review Article | Published:

The human microbiome: at the interface of health and disease

Nature Reviews Genetics volume 13, pages 260270 (2012) | Download Citation

Abstract

Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.

Key points

  • The human microbiome and its relationship to disease is a new and rapidly evolving field of study.

  • The co-evolution between hosts and their microbiomes has led to cooperative interactions in metabolism and homeostasis.

  • Concepts from community ecology — such as resilience, community disturbances and extinction — are useful in understanding the microbiome.

  • New computational and statistical tools are being developed to analyse the large sequence data sets that are generated by the increasingly powerful technologies.

  • The taxonomic composition and functional characteristics of the microbiome may allow individuals to be categorized into different microbial patterns, called enterotypes, in the gastrointestinal tract. Although low-level taxonomy varies substantially among individuals, higher-level taxonomy and functional characteristics seem to be largely preserved.

  • Many factors affect the composition of the microbiome over the course of a human lifetime. These include inheritance, the mode of infant delivery, diet and age-related changes in adults.

  • The relationships between the microbiome and several human diseases are being intensively studied for conditions that include colorectal cancer, inflammatory bowel disease and immunologically mediated skin diseases.

  • Causal relationships for many of the associations between the microbiome and disease states have yet to be proven.

  • Understanding the links between the microbiome and human disease may provide prophylactic or therapeutic tools to improve human health.

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Acknowledgements

This work was supported by NIH grants R01GM63270, R01DK090989, UH2 AR057506, 5 P30 CA016087 and 1UL1RR029893, the Diane Belfer Program for Human Microecology, the Michael Saperstein Medical Scholars Fund and the Levin Fellowship in Gastroenterology.

Author information

Affiliations

  1. Department of Medicine, NYU Langone Medical Center, New York, New York 10016, USA.

    • Ilseung Cho
    •  & Martin J. Blaser
  2. New York Harbor Department of Veterans Affairs Medical Center (Manhattan), New York, New York 10010, USA.

    • Ilseung Cho
    •  & Martin J. Blaser
  3. Department of Microbiology, NYU Langone Medical Center, New York, New York 10016, USA.

    • Martin J. Blaser
  4. Department of Biology, New York University, New York, New York 10003, USA.

    • Martin J. Blaser

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  2. Search for Martin J. Blaser in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ilseung Cho.

Glossary

Microbiota

The microbial organisms that constitute the microbiome. The composition of the microbiota in a community can vary substantially between environmental sites, among host niches and between health and disease.

16S ribosomal RNA

A component of the 30S small subunit of prokaryotic ribosomes. Sequencing of the 16S rRNA has been used to identify prokaryotic taxonomy in complete environmental samples such as the microbiome.

Microbiome

The totality of microbes, their genetic information and the milieu in which they interact. Microbiomes typically consist of environmental or biological niches containing complex communities of microbes.

Metagenome

The genetic information of a complex population — typically from microbes in an environmental or host niche sample — that is constituted by the genomes of many individual organisms. The metagenome provides information about the functional genetic potential of the aggregate population.

Extinction

The loss of an organism or group of organisms (usually of a species) from an ecosystem.

Enterotype

A recently proposed classification unit of animals that is based on the bacteriological composition of their gut microbiome. There are reported to be at least three distinct enterotypes, which are independent of ethnic background and diet.

Nash equilibria

Concepts from game theory in which players know the strategies of the others, and in which any change from their strategy puts them in a less favourable position.

Resilience

A term in ecology indicating the capacity of a system to absorb disturbance and to reorganize itself while undergoing change, so as to retain essentially the same function, structure and identity.

Extirpations

The loss of species in a locality (for example, an individual host).

Allelopathy

A phenomenon in which a microbe uses chemical means to aid its competition within a group of microbes. Allelopathy may involve manipulation of third parties (for example, the host) to favour competition.

Mating preference

The selection or choice of sexual partners that is often based on traits of a potential mate. Genetic differences between selected and non-selected hosts are a source of selectable variation.

Antecubital fossae

The triangular areas on the anterior (flexor) aspects of elbow joints.

Popliteal fossae

The shallow depressions that are found on the flexor aspects of knee joints.

Pilosebaceous units

The anatomic structure around each hair shaft that consists of the hair shaft and follicle, the sebaceous gland and the erector pili muscle.

Amphibiont

An organism (for example, a microbe) that may have a pathogenic or symbiotic relationship with another organism (for example, its host), depending on context. This is a more specific term than commensal.

Lamina propria

A thin layer of loose connective tissue that lies underneath the epithelium; collectively these tissues constitute the mucosa that line various lumens in the body. The lamina propria is densely populated by immunological and inflammatory cells.

Steatosis

The pathological accumulation and retention of lipids in liver parenchymal cells. Substantial steatosis can compromise cellular functions and is associated with disease processes, including alcoholism, diabetes and hyperlipidaemia.

Commensals

Organisms (for example, microbes) that are involved in a form of symbiosis in which one organism derives a benefit while the other is unaffected.

Probiotic

Living microorganisms that are thought to confer a benefit to the host.

Roux-en-Y surgery

A type of gastric bypass surgery that is primarily used for the treatment of morbid obesity. In Roux-en-Y surgeries, a portion of the small bowel is bypassed to decrease the absorption of nutrients.

Dysbiosis

A condition in which the normal microbiome population structure is disturbed, often through external pressures such as disease states or medications.

Gnotobiotic

Describes an animal that is colonized solely by known strains of bacteria or other microorganisms. The term also describes germ-free animals, as the status of their microbial communities is known.

Conventionalization

A method in which germ-free animals (particularly mice) are inoculated with gut microbiota to populate the gastrointestinal tract.

Prebiotics

Food ingredients that confer specific changes in the gut microbiome and lead to beneficial effects in the host.

Operational taxonomic unit

(OTU). The smallest phylogenetic unit described by variations in 16S ribosomal RNA sequencing. Dissimilarity of <1% in 16S rRNA sequences has commonly been used to define an OTU but <3% and <5% have also been used.

Non-coexistence

An exclusivity scenario in which the abundance of one species leads to another species being less abundant than would be expected by chance.

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