Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function
Abstract
:1. Introduction
2. Key Elements in Barrier Permeability
3. Regulation of Barrier Permeability by the Gut Microbiome
4. Infections and Gastrointestinal Permeability
4.1. Tight Junction Protein Degradation and Reorganisation
4.2. Activation of Host Cell Signalling Pathways
4.3. Cell Cytoskeleton Alteration
5. Leaky Gut and Diseases
5.1. Inflammatory Bowel Diseases (IBDs)
5.2. Rheumatic Diseases
5.3. Metabolic Diseases
6. Therapy-Induced Epithelial Barrier Dysfunction
6.1. Radiation Enteritis
6.2. Chemotherapy-Induced Gut Toxicity
6.3. Graft-versus-Host Disease
7. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
References
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Gut Permeability Alteration | Pathogen | Mechanism |
---|---|---|
Tight junction protein degradation and reorganisation | Campylobater jejuni [68,69] | Cleavage of occludin and E-cadherine proteins by HtrA |
Clostridium perfringens [68,69,70,71,72,73,74,75] | TJ destruction by direct enterotoxin binding with claudin 4 | |
Entamoeba histolytica [68,69,70,71,72,73,74,75] | TJ destruction by direct enterotoxin binding with claudin 1 and 2 | |
Vibrio cholerae [59,76,77,78] | CTA modulation of chloride ion channels | |
ZOT modulation of TJ proteins in small intestine | ||
Degradation of TJ proteins and TJ morphology rearrangement by Ha/P proteinase | ||
Alteration of host cell signalling pathways associated with TJ complex | Enteropathogenic Escherichia coli [79] | Occludin re-arrangement by cGMP and PKA formation triggered by enteropathogenic E. coli enterotoxin A |
Shigella flexneri [78,80] | Alteration of claudin 2 and 4, occluding and ZO-1 proteins by modulation of ERK1/2 | |
Campylobacter concinus [79,80,81] | TJ pathway regulation similar to V. cholerae ZOT | |
E. coli [79,80,81] | ||
Coxsackievirus, Adenovirus [81,82] | TJ disruption by occluding internalisation due to CAR | |
Rotavirus [82] | TJ disruption and cellular entry due to JAM-A | |
Cell cytoskeleton alteration | Samonella sp. [59,60,83,84] | Actin alteration via SopB, SopE, SopE2, SipA and Rho GTPases pathway |
E. coli [66,85] | Actin/myosin contraction via EspF, EspH, Tir and MLCK processes | |
Aspergillus and Penicillium [86] | F-actin filament disruption |
Changes in Gut Epithelial Barrier | Patients/Experimental Models | |
---|---|---|
Inflammatory bowel diseases | Occludin downregulation [92] | IBD patients |
Claudin 1 and claudin 4 upregulation [93] | IBD patients | |
Cingulin downregulation [94] | UC patients | |
Higher bacterial counts in mucosal layer [95] | IBD patients | |
F. nucleatum regulates the expression and distribution of ZO-1 and occludin [96] | IBD patients/DSS model | |
B. vulgatus alters ZO-1 and occludin [97] | IBD patients/IL-10 deficient mice | |
Claudin 7 degradation by MMP-7 [98] | Colitis mouse model | |
Reduction in the level of IPA, which improves barrier function [44,99] | IBD patients | |
Downregulation of cholic acid, which is important for intestinal stem cell renewal [100] | IBD patients/colitic mice | |
Reduced expression of ACF7, important for cytoskeletal stability [101] | UC patients/DSS mouse model | |
GGTase1 deficiency, leading to increased permeability [102] | Mouse model | |
Reduced expression of DNMT3A, important for epithelial structural regulation [103] | CD patients/mouse | |
Autophagy, important for regulation of barrier functions, are associated with CD susceptibility [104,105,106,107,108,109,110] | CD patients | |
Downregulated colonic expression of BRG1, important for regulating ROS levels and protecting the epithelial barrier [111] | IBD patients/mouse | |
Rheumatic diseases | Reduced expression of occludin and claudin-1 [112] | RA patients |
Collinsella aerofaciens reduces the expression of ZO-1 and occludin and increase disease severity [113] | In vitro/mouse RA model | |
Increased abundance of Enterobacteriaceae increase gut permeability [114] | RA patients | |
Reduced abundance of barrier protective Bifidobacterium adolescentis, Bifidobacterium longum and Faecalibacterium prausnitzii [114] | RA patients | |
Subclinical gut inflammation and dysbiosis [115,116,117] | AS and PsA patients | |
Reduced epithelial expression of claudin 1, claudin 4, occludin and ZO-1 [118] | AS patients | |
Increased gut permeability intensifies disease severity [119] | SLE mouse model | |
Metabolic diseases | Reduced expression of claudin-1, claudin-3 and JAM-1, and increased gut permeability [120] | HFD-fed mouse model |
Hyperglycaemia alters barrier integrity [121] | Mouse model/in vitro | |
High glucose and high fructose diets increased gut permeability and reduce the expression of occludin and ZO-1 [122] | Mouse model | |
Increased abundance of Enterobacteriales, correlated with increased colonic permeability [123] | Type II diabetes patients |
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Schreiber, F.; Balas, I.; Robinson, M.J.; Bakdash, G. Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function. Cells 2024, 13, 477. https://doi.org/10.3390/cells13060477
Schreiber F, Balas I, Robinson MJ, Bakdash G. Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function. Cells. 2024; 13(6):477. https://doi.org/10.3390/cells13060477
Chicago/Turabian StyleSchreiber, Fernanda, Iulia Balas, Matthew J. Robinson, and Ghaith Bakdash. 2024. "Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function" Cells 13, no. 6: 477. https://doi.org/10.3390/cells13060477