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Review
. 2013 Apr;14(4):319-27.
doi: 10.1038/embor.2013.27. Epub 2013 Mar 12.

The dynamics of gut-associated microbial communities during inflammation

Sebastian E Winter  1 , Christopher A Lopez, Andreas J Bäumler
Affiliations
Review

V体育ios版 - The dynamics of gut-associated microbial communities during inflammation

Sebastian E Winter et al. EMBO Rep. 2013 Apr.

Abstract

Our intestine is host to a large microbial community (microbiota) that educates the immune system and confers niche protection. Profiling of the gut-associated microbial community reveals a dominance of obligate anaerobic bacteria in healthy individuals. However, intestinal inflammation is associated with a disturbance of the microbiota-known as dysbiosis-that often includes an increased prevalence of facultative anaerobic bacteria VSports手机版. This group contains potentially harmful bacterial species, the bloom of which can further exacerbate inflammation. Here, we review the mechanisms that generate changes in the microbial community structure during inflammation. One emerging concept is that electron acceptors generated as by-products of the host inflammatory response feed facultative anaerobic bacteria selectively, thereby increasing their prevalence within the community. This new paradigm has broad implications for understanding dysbiosis during gut inflammation and identifies potential targets for intervention strategies. .

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Carbohydrate acquisition strategies of Clostridia, Bacteroidia and Enterobacteriaceae. The transport of carbohydrate across the cytoplasmic membrane (CM) is typically mediated by ATP-binding cassette (ABC) transporters. These contain either periplasmic binding proteins (PBPs), present in Gram-negative bacteria (shown in panels B and C), or a membrane-anchored lipoprotein involved in binding (L), present in Gram-positive bacteria (shown in panel A), a transmembrane transporter (TM) and membrane-associated nucleotide-binding proteins (Ns) involved in energizing transport by mediating hydrolysis of ATP. Bacteroidia use outer membrane proteins (BPs) to bind carbohydrate, which is degraded into oligosaccharides using glycoside hydrolases (Hs). The resulting oligosaccharides are transported by an energy-coupled outer membrane transporter (ECT) in a process energized through the proton motive force generated by the TonB ExbBD proteins. Enterobacteriaceae rely on outer membrane diffusion channels (ODCs) for passive transport of oligosaccharides across the outer membrane (OM) along a concentration gradient. CS, cytosol; EM, extracellular milieu; ExbBD, excretion of enterobactin gene B/D; PP, periplasmic space; TonB, phage T1 resistance locus B.
Figure 2
Figure 2
Phylum-level changes in the microbiota composition on intestinal inflammation. Inflammatory infiltrates—such as neutrophils, and cytokines—such as IFN-γ, are a source of or induce the expression of enzymes (iNOS, NOX1, DUOX2, PHOX, SOD and MPO) that generate antimicrobial radicals, such as superoxide, peroxide, hypochloride, nitric oxide and peroxynitrite. In the intestinal lumen, these radicals react to form harmless oxidation products—such as nitrate, N-oxides or S-oxides—that serve as electron acceptors. These support the growth of facultative anaerobic bacteria by anaerobic respiration. The resulting outgrowth of facultative anaerobic bacteria gives rise to phylum-level changes in the microbiota composition, including an increased relative abundance of Enterobacteriaceae and a marked decrease in obligate anaerobic Clostridia and Bacteroidia. DMSO, dimethyl S-oxide; DUOX2, dual function NAD(P)H oxidase 2; IFN-γ, interferon gamma; iNOS, inducible nitric oxide synthase; MPO, myeloperoxidase; NOX1, NADPH oxidase 1; PHOX, phagocyte NADPH oxidase; SOD, superoxide dismutase; TMAO, trimethylamine N-oxide.
Figure 3
Figure 3
Selective forces driving the evolution of pathogenic Enterobacteriaceae species. (A) The genus Salmonella comprises enteric pathogens that are closely related to commensal Escherichia coli, with whom they have a common ancestor as indicated by the schematic drawing of their phylogenetic tree (not to scale). The timing of horizontal gene transfer events introducing virulence factors or fitness factors is indicated. Acquisition of the indicated DNA regions conferred the ability to induce inflammation, benefit from the resulting host response and enhance their transmission. (B) The images show the natural habitat of commensal E. coli (normal intestine, top panel) and of pathogenic Salmonella species (inflamed intestine, bottom panel). The images of calf intestine were reproduced from [112] with permission. SPI1/2/4/5; Salmonella pathogenicity island 1/2/4/5.
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Sebastian E Winter, Andreas J Bäumler & Christopher A Lopez
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