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Gut homeostasis in a microbial world: insights from Drosophila melanogaster

Key Points

  • Drosophila melanogaster feeds on microorganisms and lives in microorganism-rich environments. However, the D. melanogaster gut is an environment of relatively low bacterial diversity, with Lactobacillus and Acetobacter spp. being the most commonly associated species.

  • Bacteria associated with D. melanogaster affect larval growth and adult stem cell activity.

  • Antimicrobial peptide production by the immune deficiency (Imd) pathway and reactive oxygen species (ROS) production by the NADPH oxidase Duox provide two complementary inducible defence mechanisms in the gut.

  • Negative regulators of the Imd pathway ensure that there is an adequate level of immune reactivity to both the gut microbiota and infectious bacteria.

  • Stress and repair mechanisms that maintain tissue integrity contribute to gut homeostasis in response to pathogens.

  • Entomopathogens can kill the host by disrupting or avoiding immune and repair mechanisms.

Abstract

Intestinal homeostasis is achieved, in part, by the integration of a complex set of mechanisms that eliminate pathogens and tolerate the indigenous microbiota. Drosophila melanogaster feeds on microorganism-enriched matter and therefore has developed efficient mechanisms to control ingested microorganisms. Regulatory mechanisms ensure an appropriate level of immune reactivity in the gut to accommodate the presence of beneficial and dietary microorganisms, while allowing effective immune responses to clear pathogens. Maintenance of D. melanogaster gut homeostasis also involves regeneration of the intestine to repair damage associated with infection. Entomopathogenic bacteria have developed common strategies to subvert these defence mechanisms and kill their host.

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Figure 1: Immune and repair mechanisms contribute to the resolution of infection.
Figure 2: Regulation of the immune deficiency pathway in the Drosophila melanogaster midgut.
Figure 3: Regulation of reactive oxygen species production in the Drosophila melanogaster midgut.
Figure 4: Epithelial renewal establishes a homeostatic loop required to tolerate infection.

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Acknowledgements

This work was supported by the Bettencourt-Scheller Foundation, a European Research Council Advanced Grant, the Swiss National Fund (grant 3100A0-12079/1) and a Human Frontier Science Program Long-term Postdoctoral Fellowship (to N.A.B.).

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Correspondence to Nicolas Buchon, Nichole A. Broderick or Bruno Lemaitre.

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Glossary

Axenic

Pertaining to animals: raised under sterile conditions.

Mitotic index

The proportion of proliferating cells in a tissue.

Ectoderm

The outermost germ cell layer in the metazoan embryo.

Endoderm

The innermost germ cell layer in the metazoan embryo.

Haemolymph

The circulatory fluid of arthropods.

Type III secretion systems

Specialized syringe-like bacterial structures that inject effectors into host cells.

Brush border

The microvillus-covered surface of the epithelium.

Pattern recognition receptors

Host receptors (such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs)) that can sense pathogen-associated molecular patterns and initiate signalling cascades which lead to an innate immune response. These receptors can be membrane bound (such as TLRs) or soluble and cytoplasmic (such as NLRs).

Peptidoglycan recognition protein

(PGRPs). Pattern recognition receptors that bind peptidoglycan from the cell wall of bacteria. Recognition PGRPs bind peptidoglycan and activate the immune response. Catalytic PGRPs degrade peptidoglycan and thereby act either as negative regulators of the immune response or as immune effectors.

Sclerotization

The process of cuticle hardening in insects.

Cardia

A valve-like structure that separates the fore- and midgut in insects.

Dysbiosis

The condition that results from an imbalance in the microbiota.

Fat body

An insect organ with immune and metabolic functions similar to those of the mammalian liver and adipose tissue.

Haemocoel

The haemolymph-containing body cavity of insects.

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Buchon, N., Broderick, N. & Lemaitre, B. Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat Rev Microbiol 11, 615–626 (2013). https://doi.org/10.1038/nrmicro3074

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