Animals are closely associated with a vast and diverse microbiota, most members of which reside in the gastrointestinal tract. Two gradients of microbial distribution exist in the gastrointestinal tract: the proximal–distal axis and the tissue–lumen axis.
Several parameters, including diet, lifestyle, antibiotics and other drugs, hygiene, and the genetics and immune status of the host, shape the microbiota composition, with various consequences for host physiology.
The gut microbiota is required for the development and maturation of the intestinal epithelium and immune system of the host. This microbiota affects properties of the mucus layer, promotes the development of lymphoid structures, modulates activation and differentiation of several lymphocyte populations and balances the production of immunoglobulin A and antimicrobial peptides.
The gut microbiota facilitates host metabolism and adiposity by expanding nutrient sources, producing essential vitamins and carrying out xenobiotic metabolism, but also affects a wide range of other host physiological aspects, including organ morphogenesis, intestinal vascularization, tissue homeostasis, carcinogenesis, bone mass and behaviour.
There is increasing evidence for a tight cross-species homeostatic interaction between the host and its microbiota, and research in this field has been facilitated by recent progress in the description and isolation of gut microbiota members, as well as in gnotobiology and host genetics. Elucidation of the molecular targets and causative connections in these host–microbiota interactions promises to reveal new possibilities to treat chronic inflammatory diseases and maintain human health.
Establishing and maintaining beneficial interactions between the host and its associated microbiota are key requirements for host health. Although the gut microbiota has previously been studied in the context of inflammatory diseases, it has recently become clear that this microbial community has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism. The underlying molecular mechanisms of host–microorganism interactions remain largely unknown, but recent studies have begun to identify the key signalling pathways of the cross-species homeostatic regulation between the gut microbiota and its host.
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The authors thank R. Perkins for editing the manuscript and A. Hallén for contributions to the figures. Work in the Bäckhed laboratory is supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation, the Swedish Heart Lung foundation, the Swedish Diabetes Foundation, the European Union-funded project TORNADO (grant FP7-KBBE-222720), Ragnar Söderberg's Foundation, Torsten Söderberg's Foundation, the NovoNordisk Foundation, AFA Insurance, IngaBritt and Arne Lundberg's Foundation and a LUA-ALF grant from the Swedish Västra Götalandsregionen.
F.B. is a scientific founder of MetaboGen AB and owns equity in the company. F.S. declares no competing financial interests.
The sum of all microorganisms (including bacteria, archaea, eukaryotes and viruses) that reside in and/or on a host or a specified part of a host (such as the gastrointestinal tract).
Pertaining to a relationship between two organisms: beneficial to both organisms. The term originates from the Latin word mutuus (lent, borrowed or mutual).
A term that extends the classical biological definition of an organism (a living system capable of autonomous metabolism and reproduction) by including the many microorganisms that live in and on that host organism, thus yielding a superior degree of complexity. The term originates from the Latin supra (above) and the Greek organon (organ, instrument, tool).
Any close physical association between two organisms, usually from different species. This includes mutualism, commensalism and parasitism. The term originates from the Greek words syn (together) and bio (life).
Normally harmless microorganism that can become pathogens under certain environmental conditions.
- Somatic hypermutation
A programmed process of mutation affecting the variable regions of immunoglobulin genes during affinity maturation of B cell receptors.
- Experimental autoimmune encephalomyelitis
An animal model of T cell-mediated autoimmune disease in general and in particular of demyelinating diseases of the central nervous system, such as multiple sclerosis.
- T follicular helper cells
A T cell subtype that resides in the B cell follicles of secondary lymphoid organs and expresses the B cell homing receptor CXC-chemokine receptor 5. These T cells mediate B cell activation and trigger the formation of the germinal centre.
- Crypts of Lieberkühn
Tubular invaginations of the intestinal epithelium around the villi. The crypt base contains Paneth cells, which secrete mainly antimicrobial peptides as well as other immune factors, and continually dividing stem cells that are the source of all intestinal epithelial cells.
- Xenobiotic metabolism
The metabolism of foreign compounds that are neither produced by nor naturally found in the host, such as drugs.
- Enterochromaffin cells
A subtype of enteroendocrine cells in the intestinal or respiratory epithelium. Enterochromaffin cells are the main source of serotonin in the body and are thereby involved in the regulation of intestinal peristalsis and nausea.
A type of junctional complex that is mainly found in epithelia (specifically, in the lateral plasma membrane of the epithelial cell) and mediates cell-to-cell adhesion to allow cells to withstand shearing forces.
- Tight junctions
Junctional complexes that are present only in vertebrates (the invertebrate equivalents are the septate junctions) and are located at the transition of the apical and lateral membrane, closely connecting two epithelial cells and thereby making the epithelium impermeable to water and solutes.
An imbalance in the structural and/or functional configuration of the microbiota, leading to a disruption of host–microorganism homeostasis.
Pertaining to an organism: associated with a defined microbiota. For example, laboratory mice can be reared under sterile (germ-free) conditions or colonized with a specific collection of microorganisms. From the Greek gnosis (known or knowledge) and bios (life).
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Sommer, F., Bäckhed, F. The gut microbiota — masters of host development and physiology. Nat Rev Microbiol 11, 227–238 (2013) doi:10.1038/nrmicro2974
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