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Review
. 2009 May;9(5):313-23.
doi: 10.1038/nri2515.

The gut microbiota shapes intestinal immune responses during health and disease (VSports在线直播)

June L Round  1 , Sarkis K Mazmanian
Affiliations
Review

The gut microbiota shapes intestinal immune responses during health and disease

June L Round et al. Nat Rev Immunol. 2009 May.

"V体育官网" Erratum in

  • Nat Rev Immunol. 2009 Aug;9(8):600

Abstract

Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer VSports手机版. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host-symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturbances in the bacterial microbiota result in dysregulation of adaptive immune cells, and this may underlie disorders such as inflammatory bowel disease. This raises the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms. .

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Figures (VSports手机版)

Figure 1
Figure 1. Model for Bacteroides fragilis-mediated protection from disease induced by Helicobacter hepaticus
B. fragilis produces an immunomodulatory polysaccharide (PSA) that induces an immunoregulatory programme that provides protection from inflammation induced by H. hepaticus. PSA is taken up by intestinal dendritic cells (DCs), which presumably migrate to the local mesenteric lymph nodes (MLNs) where they initiate T-cell responses by presenting PSA on MHC class II molecules to CD4+ T cells. This process helps to restore a balanced T helper (TH) and regulatory T (TReg) cell profile. Subsequently, naive TH cells adopt anti-inflammatory functions that include expression of interleukin-10 (IL-10). IL-10 is required to suppress the production of pro-inflammatory cytokines (such as IL-17, IL-23 and tumour-necrosis factor (TNF) induced by H. hepaticus during experimental colitis. It is this balance of the pro-inflammatory responses to H. hepaticus by regulation induced by B. fragilis that results in the control of intestinal inflammation.
Figure 2
Figure 2. Immunological dysregulation is the result of dysbiosis in the microbiota
a | A healthy microbiota contains a balanced composition of multiple classes of bacteria. Commensals are permanent residents of this complex ecosystem and provide no benefit or detriment to the host (at least to our knowledge). Symbionts are organisms with known health-promoting functions. Pathobionts are also permanent residents of the microbiota with the potential to induce pathology. b | During dysbiosis, there is an unnatural shift in the composition of the microbiota whereby either the numbers of symbionts are reduced and/or pathobionts are increased. The various causes for this are not entirely clear, but are likely to include recent societal advances in developed countries. The result is non-specific inflammation which may predispose certain genetically susceptible people to inflammatory disease. Pathogens are opportunistic organisms that cause rare and acute inflammation.
Figure 3
Figure 3. Proposed causes of Dysbiosis
We propose the notion that the composition of the microbiota can shape a healthy immune response or predispose to disease. Multiple factors can contribute to a dysbiotic state including host genetics, medical practices, life style, and exposure. a| Host genetics can potentially influence dysbiosis in multiple ways. Genome wide association studies of IBD patients have revealed polymorphisms in immune-related genes. An individual lacking genetic regulatory mechanisms or overactive pro-inflammatory pathways will have an intestinal environment marked by unchecked inflammation. Studies have demonstrated the ability of inflammation alone to influence the composition of the microbiota, potentially in favor of pathobionts. Alternatively, it is possible that genetics of the host can ‘select’ or exclude the colonization of particular organisms. This selection can be either active (as would be the case of an organism recognizing a particular receptor on the host) or passive (the host environment is more conducive to fostering the growth of select organisms). ‘Selection’ of pathobionts by the host could tip the balance in favor of inflammation. b| The food we consume and even the day-to-day stress represent aspects of life style that have the potential to influence the microbiota. c| Hospitals represent a sterile environment in which infants are born. While the sterility protects from dangerous pathogens, it also has the potential to prevent early exposure to health-promoting bacteria. d| The advent of antibiotics represents a major medical breakthrough; however, antibiotics do not have the capacity to distinguish between pathogenic or symbiotic microorganism s and may adversely alter the microbiota.
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References

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