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The immune system and the gut microbiota: friends or foes?


The mammalian intestine is home to a complex community of trillions of bacteria that are engaged in a dynamic interaction with the host immune system. Determining the principles that govern host–microbiota relationships is the focus of intense research. Here, we describe how the intestinal microbiota is able to influence the balance between pro-inflammatory and regulatory responses and shape the host's immune system. We suggest that improving our understanding of the intestinal microbiota has therapeutic implications, not only for intestinal immunopathologies but also for systemic immune diseases.

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Figure 1: Modulation of intestinal epithelial cell pro-inflammatory responses by the microbiota.
Figure 2: Modulation of adaptive immune responses in the gut by the microbiota.
Figure 3: Effects of SFB colonization on the immune system.
Figure 4: Schematic representation of host–microbiota interactions in the healthy and inflamed gut.


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The authors thank W. Garrett for sharing unpublished data. Their work is supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut National de la Recherche Agronomique (INRA) and the Agence Nationale de la Recherche and Fondation Princesse Grace. The authors are partners of the European Community networks Cross-Talk (contract number PITN-GA-2008-215553) and Tornado (FP7 222720).

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Correspondence to Nadine Cerf-Bensussan.

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Ankylosing enthesopathy

An inflammatory autoimmune disease of the joints that naturally occurs in mice on a C57BL/10 genetic background; the disease is similar to human ankylosing spondylitis. The pathology is characterized by the proliferation of cartilage and connective tissue, which culminates in ankylosis of the joints.

Germinal centres

Highly specialized and dynamic microenvironments that are located in secondary lymphoid tissues and give rise to secondary B cell follicles during an immune response. Germinal centres are the main sites of B cell proliferation and differentiation, which leads to the generation of memory B cells and plasma cells that produce high-affinity antibodies.

Gnotobiotic mice

Germ-free mice are born and raised in sterile isolators and are devoid of colonization by any microorganisms, but after they have been experimentally colonized by known bacteria, they are said to be gnotobiotic. They are kept in isolators to control their bacterial status.

IgE-associated allergies

Type 1 hypersensitivity reactions that are mediated by IgE, which induces mast cell activation and degranulation. Such immune reactions are seen in asthma, allergic rhinitis, systemic anaphylaxis and food allergies.

Obligate and facultative symbionts

Obligate microbial symbionts need to colonize a host to develop and multiply, unlike facultative microbial symbionts, which can also develop outside a host.


Microbial symbionts that can cause defined disease in predisposed hosts following changes in the gastrointestinal environment.


The whole genome of all of the microorganisms that colonize a specific environment.

Peyer's patches

Collections of lymphoid follicles that are located in the intestinal mucosa and are particularly abundant in the ileal mucosa. Together with mesenteric lymph nodes, they form the inductive compartment for intestinal immune responses.


Gram-negative microorganisms that colonize very distinct environments and are the second largest group of bacteria on earth. Proteobacteria that colonize the intestine include commensal, pathogenic and opportunistic species, such as Salmonella, Shigella and Helicobacter spp. and Escherichia coli strains. In healthy adults, proteobacteria represent less than 1% of the enteric microbiota, but they are a major cause of intestinal and extraintestinal diseases.

Type VI secretion system

(T6SS). Like T3SS and T4SS, T6SS is a multi-subunit complex that acts like a 'needle and syringe' to translocate bacterial products across the double-membrane of Gram-negative bacteria into the cytoplasm of eukaryotic cells.


Chemical compounds that are foreign to a living organism and that can be toxic, even at low concentrations.

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Cerf-Bensussan, N., Gaboriau-Routhiau, V. The immune system and the gut microbiota: friends or foes?. Nat Rev Immunol 10, 735–744 (2010).

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