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Review
. 2014 Mar:68:122-33.
doi: 10.1016/j.freeradbiomed.2013.11.008. Epub 2013 Nov 22.

Role of the enteric microbiota in intestinal homeostasis and inflammation

Iurii Koboziev  1 , Cynthia Reinoso Webb  1 , Kathryn L Furr  1 , Matthew B Grisham  2
Affiliations
Review

Role of the enteric microbiota in intestinal homeostasis and inflammation

Iurii Koboziev et al. Free Radic Biol Med. 2014 Mar.

Abstract

The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10(14)) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.

Keywords: Commensal bacteria; Crohn disease; Dysbiosis; Fecal transplant; Free radicals; Inflammatory bowel disease; Pathobiont; Regulatory T cells; Symbiont; Th1 effector cells; Th17 effector cells; Ulcerative colitis.

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Figures

Figure 1
Figure 1. Composition and luminal concentrations of the major microbial species in different regions of the gastrointestinal tract
Box panels show the numbers of organisms/gram luminal contents (Reproduced from reference 5, with permission).
Figure 2
Figure 2. Systemic and intestinal immune responses to enteric bacteria and their antigens
Luminal intestinal bacteria and/or antigens (Ag) enter the Peyer's patches (PPs) via transport by the M cells where they are endocytosed by dendric cells (DCs) within the sub-epithelial dome region. Bacteria and Ag-loaded DCs may then interact with T and B cells within the PPs to prime the T and B cells or they may migrate from the PPs to the gut-draining mesenteric lymph nodes (MLNs) by way of the afferent lymphatics. Naïve T-cells (colored in green) that enter the MLNs will interact with these DCs resulting in the priming, polarization and expansion of the T-cells to yield effector cells (colored in red). These effector T cells then exit the MLNs via the efferent lymphatics, return to the systemic circulation and home to the gut lamina propria. Enteric bacteria and antigens may also be endocytosed by DCs located within the gut lamina propria and migrate to the MLNs via the afferent lymphatics. BCF refers to B cell follicle (Modified from reference 55, with permission).
Figure 3
Figure 3. Adaptive and innate immune responses to invading bacteria
A). Enteric antigen-activated Th1 and Th17 effector T-cells produce large amounts of inflammatory cytokines such as IFN-γ, IL-17 and TNF-α within the intestinal lamina propria. These inflammatory cytokines interact with and activate antigen presenting cells (APC) and tissue macrophages (MΦ) to produce additional inflammatory mediators including IL-1β, IL-6, IL-8, and IL-12 as well as a variety of reactive oxygen and nitrogen species including superoxide (O2−), hydrogen peroxide (H2O2) and nitric oxide (NO). Together, these mediators enhance the microbicidal activity of tissue macrophages thereby “helping” these phagocytes destroy the invading microbes. In addition, many of these mediators are known to enhance the expression of different adhesion molecules (e.g. ICAM-1,VCAM-1 and E-selectin) on the surface of the post-capillary endothelial cells thereby facilitating the recruitment of additional leukocytes (e.g. neutrophils, monocytes, lymphocytes) into the intestinal tissue to help in killing bacteria. Under normal circumstances, these immune responses are tightly regulated to limit the development of inflammatory tissue injury that may accompany these protective responses. B). In the absence of appropriate regulatory mechanisms, the sustained, overproduction of the different inflammatory mediators promote epithelial and endothelial injury and dysfunction leading to erosions, ulcerations, fibrosis and edema.
Figure 3
Figure 3. Adaptive and innate immune responses to invading bacteria
A). Enteric antigen-activated Th1 and Th17 effector T-cells produce large amounts of inflammatory cytokines such as IFN-γ, IL-17 and TNF-α within the intestinal lamina propria. These inflammatory cytokines interact with and activate antigen presenting cells (APC) and tissue macrophages (MΦ) to produce additional inflammatory mediators including IL-1β, IL-6, IL-8, and IL-12 as well as a variety of reactive oxygen and nitrogen species including superoxide (O2−), hydrogen peroxide (H2O2) and nitric oxide (NO). Together, these mediators enhance the microbicidal activity of tissue macrophages thereby “helping” these phagocytes destroy the invading microbes. In addition, many of these mediators are known to enhance the expression of different adhesion molecules (e.g. ICAM-1,VCAM-1 and E-selectin) on the surface of the post-capillary endothelial cells thereby facilitating the recruitment of additional leukocytes (e.g. neutrophils, monocytes, lymphocytes) into the intestinal tissue to help in killing bacteria. Under normal circumstances, these immune responses are tightly regulated to limit the development of inflammatory tissue injury that may accompany these protective responses. B). In the absence of appropriate regulatory mechanisms, the sustained, overproduction of the different inflammatory mediators promote epithelial and endothelial injury and dysfunction leading to erosions, ulcerations, fibrosis and edema.
Figure 4
Figure 4. Distribution of predominant bacterial phylotypes in the human intestinal tract
These figures illustrate the relative abundance as a function of location along the healthy and inflamed small bowel (ileum) and colon. (Reproduced from reference 92, with permission).
Figure 5
Figure 5
Autoimmune and chronic inflammatory diseases in which the intestinal microbiota has been implicated.
Figure 6
Figure 6. Immunological dysregulation associated with dysbiosis of the microbiota
A) A healthy microbiota contains a balanced composition of different classes of bacteria. Symbionts are organisms with known health-promoting functions. Commensals are permanent residents of this complex ecosystem and provide no benefit or detriment to the host. Pathobionts are also permanent residents of the microbiota and have the potential to induce pathology. B) Dysbiosis is created by an alteration in the composition of the microbiota resulting in either a reduction in the numbers of symbionts and commensal and/or an increase in the numbers of pathobionts. This may result in the induction of inflammation in genetically susceptible individuals (Modified from reference 121, with permission).
Figure 7
Figure 7. Potential therapeutic strategies for modulating intestinal dysbiosis
(Modified from reference 123, with permission).
See this image and copyright information in PMC

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References

    1. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8. - PMC - PubMed
    1. Fava F, Danese S. Intestinal microbiota in inflammatory bowel disease: friend of foe? World J Gastroenterol. 2011;17:557–66. - PMC - PubMed
    1. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837–48. - PubMed
    1. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30. - PMC - PubMed
    1. Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008;134:577–94. - PubMed

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