Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli

Shawki, Ali; McCole, Declan F.

doi:10.1016/j.jcmgh.2016.10.004

Cited by 92 publications

(77 citation statements)

References 115 publications

(157 reference statements)

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“…Epithelial barrier permeability is an important parameter of intestinal function reflecting the degree of selectivity in the transfer of nutrients across the epithelial layer and the exclusion of bacteria and other potentially harmful materials (Bischoff et al, 2014). Increases in epithelial barrier permeability occur in the setting of inflammation (Ahmad et al, 2017;Michielan and D'Incà, 2015) and infectious disease (Shawki and McCole, 2017). Colonization of HIOs with E. coli results in increased transcription of genes associated with the formation of the adherens junction and other cell-cell interactions in the epithelium (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

Hill

Fields

Mukherjee

et al. 2017

Preprint

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The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naïve epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

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Section: Discussionmentioning

confidence: 99%

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

Hill

Fields

Mukherjee

et al. 2017

Preprint

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“…Mice had not only intestinal barrier dysfunction but also cellular dysfunction. The main functions of occludin are regulation and sealing of TJs [41,42]. That ZO-1 outperformed other TJ markers may re ect the concomitant organ epithelial injury which occurs in MODS [36].…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

Gai

Wang

et al. 2020

Preprint

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Background This study aimed to confirm the existence of gut microbiota (GM) imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Methods The study included acute experiments and 7-day mortality observation experiments with clean-grade C57BL/6, and they were randomly divided randomly into three groups, namely, the sham group, the sepsis model group and the fecal microbiota transplantation group. Fresh feces from 10 mice were kept every day to make fecal liquid. The Sham group and the CLP group were given intragastric administration once a day with phosphate-buffered saline, and the FMT group mice were given fecal microbiota transplantation once a day. The animals were euthanized at 12, 24, and 48 h after modeling, and blood, colon, and stool from each mouse were collected at the same time.Results Colonic pathological scores, pro-inflammatory cytokines, TLR4/MyD88/NF-κB protein levels, and gene expression levels, were lower in the FMT group, while anti-inflammatory factors, mucus layer thickness, MUC2, occludin, and ZO-1 proteins were higher in the FMT group than the CLP group. Bacterial flora analysis showed gut flora was reconstructed after FMT. The species composition of the differential pathways revealed that the Lachnospiraceae group contributed the most by the L-lysine pathway of fermentation to acetate and butanoate.Conclusion GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

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“…Pathogenic bacteria, including Salmonella Typhimurium and invasive E. coli can target these defences by secreting proteases and neuro-immune stimulatory ligands to impair brush border formation (Lhocine et al, 2015) and disrupt epithelial tight-junctions ( Fig. 3) (Awad et al, 2017;Shawki and McCole, 2017).…”

Section: Crypt-villus Morphologymentioning

confidence: 99%

Host‐microbe interaction in the gastrointestinal tract

Parker

Lawson

Vaux

et al. 2017

Environmental Microbiology

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SummaryThe gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.

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Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli

Cited by 92 publications

References 115 publications

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

Host‐microbe interaction in the gastrointestinal tract

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