Commensal bacterial internalization by epithelial cells: An alternative portal for gut leakiness

Yu, Linda Chia-Hui

doi:10.1080/21688370.2015.1008895

Cited by 17 publications

(29 citation statements)

References 75 publications

(116 reference statements)

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“…Accumulating evidence indicated that mucosa-associated bacteria are different from fecal microbial population, and may better reflect regional changes in gut microbes at mucosal surfaces at sites of inflammation [ 50 , 53 ]. In healthy states, indigenous symbiotic bacteria mostly reside in the intestinal lumen which are separated from the epithelial cells by inner firm mucus layers [ 67 ], and are not in direct contact with the epithelial cells in physiological conditions [ 68 , 69 ]. Nevertheless, high densities of mucosa-associated bacteria were reported in IBD patients [ 64 , 65 , 70 ], and were suspected to play a more dominant role than fecal microbiota in promoting gut inflammation.…”

Section: Microbiota Dysbiosis and Mucosa-associated Bacteria In Chronmentioning

confidence: 99%

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

2018

J Biomed Sci

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299

232

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Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as colitis-associated cancers. Genetic polymorphism of innate immune receptors had long been considered a major risk factor for IBD, and the mutations were also recently observed in CRC. Altered microbial composition (termed microbiota dybiosis) and dysfunctional gut barrier manifested by epithelial hyperpermeability and high amount of mucosa-associated bacteria were observed in IBD and CRC patients. The findings suggested that aberrant immune responses to penetrating commensal microbes may play key roles in fueling disease progression. Accumulative evidence demonstrated that mucosa-associated bacteria harbored colitogenic and protumoral properties in experimental models, supporting an active role of bacteria as pathobionts (commensal-derived opportunistic pathogens). Nevertheless, the host factors involved in bacterial dysbiosis and conversion mechanisms from lumen-dwelling commensals to mucosal pathobionts remain unclear. Based on the observation of gut leakiness in patients and the evidence of epithelial hyperpermeability prior to the onset of mucosal histopathology in colitic animals, it was postulated that the epithelial barrier dysfunction associated with mucosal enrichment of specific bacterial strains may predispose the shift to disease-associated microbiota. The speculation of leaky gut as an initiating factor for microbiota dysbiosis that eventually led to pathological consequences was proposed as the “common ground hypothesis”, which will be highlighted in this review. Overall, the understanding of the core interplay between gut microbiota and epithelial barriers at early subclinical phases will shed light to novel therapeutic strategies to manage chronic inflammatory disorders and colitis-associated cancers.

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Section: Microbiota Dysbiosis and Mucosa-associated Bacteria In Chronmentioning

confidence: 99%

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

2018

J Biomed Sci

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299

232

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“…The gut commensals mostly reside in the intestinal lumen in physiological conditions, separated by the inner mucus layer and are rarely in direct contact with the epithelial cells. 53 54 55 56 The concept of bacterial adhesion to host epithelial cells was first reported in uropathogenic Escherichia coli in 1908. 57 In the past two decades, high numbers of mucosa-associated bacteria were reported in clinical studies of IBD and CRC.…”

Section: Potential Tumorigenic Pathobiontsmentioning

confidence: 99%

Impact of microbiota in colorectal carcinogenesis: lessons from experimental models

Wei

2018

Intest Res

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A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.

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“…Low doses of pro-inflammatory cytokines, such as IFN-γ, were shown not to affect TJ protein expression but to activate bacterial endocytosis by epithelial cells[ 95 ]. This process is dependent on extracellular signal-regulated kinase Cζ and ADP-ribosylation factor-6 signaling[ 96 ].…”

Section: Gut Microbiota and Metabolome In CDmentioning

confidence: 99%

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease

Cukrowská

Sowińska

Bierła

et al. 2017

WJG

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Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

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Commensal bacterial internalization by epithelial cells: An alternative portal for gut leakiness

Cited by 17 publications

References 75 publications

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Impact of microbiota in colorectal carcinogenesis: lessons from experimental models

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease

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