Epithelial glycosylation in gut homeostasis and inflammation

Goto, Yoshiyuki; Uematsu, Satoshi; Kiyono, Hiroshi

doi:10.1038/ni.3587

Cited by 145 publications

(129 citation statements)

References 95 publications

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“…2B). The α1,2-linked fucosylation is a major glycosylation detected on the surface of IECs and secreted proteins 10 . The addition of an α1,2-linked fucose to terminal galactose residues of glycan is catalysed by two α1,2-fucosyltransferases (FUT1 and FUT2).…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal fucosylation is regulated by many intestinal environmental stresses, including tissue injury, bacterial infection and inflammation 9,10 . FUT1 mediates the α1,2-linked fucosylation in M cells 15 .…”

Section: Discussionmentioning

confidence: 99%

“…The induction of α1,2-fucose in IECs was regulated by a subset of mucosal immune cells, especially group 3 innate lymphoid cells (ILC3) 10,16 , implying that α1,2-fucose in IECs act as a biological and interactive molecule for the host–microbe cross-communication.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study using microarray analysis, we reported that the expression of Fut2 , a gene encoding fucosyltransferase 2 (FUT2), was significantly decreased in the terminal ileum of mice subjected to CSDS 8 . FUT2 adds terminal α1,2-fucose residues to glycan chains and is responsible for most of the fucosylation in the mouse and human gut 9,10 .…”

Section: Introductionmentioning

confidence: 99%

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Reduced fucosylation in the distal intestinal epithelium of mice subjected to chronic social defeat stress

Omata

Aoki

Aoki-Yoshida

et al. 2018

Sci Rep

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Psychological stress can cause dysfunction of the gastrointestinal tract by regulating its interaction with central nervous system (brain-gut axis). Chronic social defeat stress (CSDS) is widely used to produce a rodent model of stress-induced human mood disorders and depression. We previously showed that CSDS significantly affects the intestinal ecosystem including cecal and fecal microbiota, intestinal gene expression profiles and cecal metabolite profiles. Here, we investigated whether the glycosylation pattern in the intestinal epithelium was affected in C57BL/6 mice exposed to CSDS (hereinafter referred to as CSDS mice). A lectin microarray analysis revealed that CSDS significantly reduced the reactivity of fucose-specific lectins (rAOL, TJA-II, rAAL, rGC2, AOL, AAL, rPAIIL and rRSIIL) with distal intestinal mucosa, but not with mucosa from proximal intestine and colon. Flow cytometric analysis confirmed the reduced TJA-II reactivity with intestinal epithelial cells in CSDS mice. In addition, distal intestine expression levels of the genes encoding fucosyltransferase 1 and 2 (Fut1 and Fut2) were downregulated in CSDS mice. These findings suggest that CSDS alters the fucosylation pattern in the distal intestinal epithelium, which could be used as a sensitive marker for CSDS exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reduced fucosylation in the distal intestinal epithelium of mice subjected to chronic social defeat stress

Omata

Aoki

Aoki-Yoshida

et al. 2018

Sci Rep

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“…Thus resident microbiota sustain continuous feedback loop mechanisms with mucosal surfaces, shaping mucosal immunity, and mechanisms of inflammation and tolerance in the gut. For example, epithelial glycosylation regulated by resident microbes and group three innate lymphoid cells (ILC3s) control commensal host symbiosis and anti microbial host responses (Goto et al, 2014, 2016). Apart from innate immune responses and Immunoglobulin A (IgA) responses, T cells also play critical roles in these processes.…”

Section: Introductionmentioning

confidence: 99%

Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection

et al. 2018

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Interactions between mucosal tissues and commensal microbes control appropriate host immune responses and inflammation, but very little is known about these interactions. Here we show that the depletion of resident bacteria using antibiotics (Abx) causes oral and gut immunopathology during oropharyngeal candidiasis (OPC) infection. Antibiotic treatment causes reduction in the frequency of Foxp3+ regulatory cells (Tregs) and IL-17A producers, with a concomitant increase in oral tissue pathology. While C. albicans (CA) is usually controlled in the oral cavity, antibiotic treatment led to CA dependent oral and gut inflammation. A combination of short chain fatty acids (SCFA) controlled the pathology in Abx treated mice, correlating to an increase in the frequency of Foxp3+, IL-17A+, and Foxp3+IL-17A+ double positive (Treg17) cells in tongue and oral draining lymph nodes. However, SCFA treatment did not fully reverse the gut inflammation suggesting that resident microbiota have SCFA independent homeostatic mechanisms in gut mucosa. We also found that SCFA potently induce Foxp3 and IL-17A expression in CD4+ T cells, depending on the cytokine milieu in vitro. Depletion of Tregs alone in FDTR mice recapitulated oral inflammation in CA infected mice, showing that Abx mediated reduction of Tregs was involved in infection induced pathology. SCFA did not control inflammation in Treg depleted mice in CA infected FDTR mice, showing that Foxp3+ T cell induction was required for the protective effect mediated by SCFA. Taken together, our data reveal that SCFA derived from resident bacteria play a critical role in controlling immunopathology by regulating T cell cytokines during mucosal infections. This study has broader implications on protective effects of resident microbiota in regulating pathological infections.

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Immunity: Regulation by the Indigenous Gastrointestinal Microbiota

Butler

2017

Encyclopedia of Life Sciences

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Human beings are colonised by a beneficial ecosystem of microorganisms collectively termed the commensal microbiota or microbiome. Predominantly found at mucosal surfaces, these organisms are most abundant in the lower gastrointestinal tract. While the majority cannot be cultured outside the body, the development of molecular biological techniques (e.g. 16S ribosomal RNA PCR and shotgun metagenomic sequencing) is now allowing investigators to explore the microbiota in unprecedented detail. Research has uncovered a complex interplay between the intestinal microbiome and the host immune system. Gnotobiotic and germ‐free animal systems have revealed an absolute requirement for commensal microbes during normal immune development, and these interactions continue to shape immunity throughout adult life. In man, alterations to the normal intestinal microbiota (termed ‘dysbiosis’) have been associated with inflammatory bowel diseases, systemic autoimmune, metabolic and even neurological disorders. Key Concepts A human being is a ‘metaorganism’ – all mucosal surfaces are colonised by commensal microorganisms, collectively termed the microbiome. Microbes are most abundant in the lower GI tract. The intestinal microbiota provides the host with vital nutrients and prevents colonisation by pathogens. Novel molecular biology techniques (e.g. 16S rRNA PCR and shotgun metagenomic sequencing) are opening up the microbiome for in‐depth study. The human microbiome project has identified >10 000 different species associated with humans with individuals carrying 200–400 species in the gut. Colonization begins in the womb, continues during birth and normally reaches equilibrium by 2–3 years of age. The microbiota regulates the intestinal immune system by stimulating the epithelial barrier, promoting release of secretory IgA by plasma B cells and inducing the development of homeostatic Th17/Treg populations in the gut mucosa. Intestinal microbes can also influence systemic immunity via the production of bioactive molecules, such as pattern recognition receptor agonists (e.g. LPS), short‐chain fatty acids, tryptophan and polyamines. Abnormal changes in the microbiota are associated with chronic inflammatory diseases, allergic inflammation, metabolic and neurological diseases.

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Epithelial glycosylation in gut homeostasis and inflammation

Cited by 145 publications

References 95 publications

Reduced fucosylation in the distal intestinal epithelium of mice subjected to chronic social defeat stress

Reduced fucosylation in the distal intestinal epithelium of mice subjected to chronic social defeat stress

Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection

Immunity: Regulation by the Indigenous Gastrointestinal Microbiota

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