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Gut biogeography of the bacterial microbiota

Key Points

  • The gut microbiota is spatially stratified along the longitudinal and cross-sectional axes of the gut. Chemical and nutrient gradients, antimicrobial peptides and physical features of the gut contribute to differences in microbial community composition in different locations.

  • The mucosal and lumenal microbiota of the gut represent distinct microbial communities. On a smaller scale, patchiness within these communities suggests that they are highly spatially organized.

  • Diet imparts a large effect on microbial colonization and relative abundance, but some bacteria can thrive independently of dietary changes by living on host-derived nutrients such as mucin glycans. Therefore, the mucus layer can harbour a reservoir of bacteria that is maintained regardless of food intake. The appendix and colonic crypts may also be examples of such microbial reservoirs.

  • Only a subset of gut symbionts are able to access the epithelial surface. Mucus, antimicrobial peptides and adaptive immune activity limit tissue accessibility. Direct interfacing between the host and microbial symbionts may be important for the maintenance of homeostasis.

  • Immunomodulation by certain symbionts allows the host to tolerate intimate relationships with potentially beneficial microorganisms. This may be a way in which commensals distinguish themselves from pathogens and prevent their elimination by the immune system.

  • Although many diseases have been associated with dysbiosis, an understanding of the function of the microbiota in health and disease requires the biogeography of the community to be considered. Recent studies in humans have found differences specific to the mucosal community in cases of inflammatory bowel disease and hepatic encephalopathy.


Animals assemble and maintain a diverse but host-specific gut microbial community. In addition to characteristic microbial compositions along the longitudinal axis of the intestines, discrete bacterial communities form in microhabitats, such as the gut lumen, colonic mucus layers and colonic crypts. In this Review, we examine how the spatial distribution of symbiotic bacteria among physical niches in the gut affects the development and maintenance of a resilient microbial ecosystem. We consider novel hypotheses for how nutrient selection, immune activation and other mechanisms control the biogeography of bacteria in the gut, and we discuss the relevance of this spatial heterogeneity to health and disease.

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Figure 1: Microbial habitats in the human lower gastrointestinal tract.
Figure 2: The mucus layers of the small intestine and colon.
Figure 3: Bacterial colonization determinants.
Figure 4: Bacterial access to the epithelium.
Figure 5: Immunomodulation by commensal gut bacteria.
Figure 6: Gut microhabitats as reservoirs of bacterial diversity.


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The authors thank E. Hsiao, B. Needham and T. Sampson for critical comments on the manuscript. G.P.D. is supported by a US National Science Foundation Graduate Research Fellowship (grant DGE-1144469). Work in the S.K.M. laboratory is supported by funding from the US National Institutes of Health (grants GM099535, DK078938 and MH100556), the Emerald Foundation and the Simons Foundation.

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Correspondence to Sarkis K. Mazmanian.

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The collection of microorganisms (including bacteria, viruses, fungi and single-celled eukaryotes) that inhabit a particular habitat, such as an animal.

Syntrophic interactions

Metabolic relationships in which one member provides nutrients to another.

Secreted immunoglobulin A

(sIgA). By far the most abundant isotype of antibody found in the gut.


A molecule that serves as a nutrient which stimulates the growth of commensal or mutualistic gut bacteria. In many cases, prebiotics can be specific for discrete groups of bacteria on the basis of their metabolic (that is, nutritional) requirements.


In ecology: organisms that participate in a close relationship with other organisms. The term encompasses organisms that participate in different types of relationship, including mutualists, commensals and parasites.


In ecology: organisms that participate in a symbiotic relationship in which one party benefits from the other without affecting the other party. Historically, commensals is also used as a term for the resident gut bacteria, although many of these may be mutualists.


In ecology: organisms that participate in a symbiotic relationship in which both parties benefit.

Gnotobiotic animals

Formerly germ-free animals that now carry a defined microbiota. The composition of the microbiota in these animals is usually determined experimentally.


The bulk of dietary fibres that is digested as it transits through the gastrointestinal tract.

Goblet cells

Specialized epithelial cells throughout the gastrointestinal tract that secrete gel-forming mucins. Goblet cells can also be present in other mucosal epithelial surfaces throughout the body.


An aggregation of bacteria that are colocalized in a matrix and reside on a surface. Biofilms may include single species of bacteria or polymicrobial communities.

Indigenous organisms

Organisms that are native to a particular habitat (also termed autochthonous), as distinct from organisms that are simply passing through a habitat (allochthonous)

Mucin 2

(MUC2). The most abundant mucin protein in the human gut; the mouse homologue is also the most abundant mouse gut mucin.

Colonization resistance

The prevention of invasion of an exogenous species into a microbial community. In the gut, colonization resistance may be a result of resource competition, spatial exclusion or direct inhibition by commensal microorganisms, or of selection mediated by host factors.

Paneth cells

Specialized epithelial cells that are found at the base of crypts in the small intestine and that secrete antimicrobial peptides.


A symbiont with the potential to promote pathology under conditions that deviate from homeostasis, such as in immunocompromised or nutrient-deprived individuals.


Pertaining to a microorganism: obligately aerobic. These microorganisms thrive only in environments with low oxygen concentrations, such as at the epithelial surface in the gut.


A deviation from a normal microbial community, such as an imbalance in the abundance, membership or localization of microorganisms.

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Donaldson, G., Lee, S. & Mazmanian, S. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol 14, 20–32 (2016).

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