Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period

Small, Cherrie; Xing, Lydia; McPhee, Joseph B.; Law, Hong T.; Coombes, Brian K.

doi:10.1371/journal.ppat.1005907

Cited by 38 publications

(32 citation statements)

References 53 publications

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“…65 In mice exposed to Salmonella typhimurium to induce acute infectious gastroenteritis, those that were colonized with an adherent-invasive Escherichia coli (AIEC) isolated from a patient with CD before exposure to S typhimurium experienced an expansion of AIEC with increased cellular and proinflammatory responses. 66 The AIEC-colonized mice also had delayed mucosal epithelial reconstitution after recovery from S typhimurium infection. These findings suggest that an episode of infectious gastroenteritis can trigger an abnormal immune response in a subject with a baseline ''susceptible gut microbiota profile.''…”

Section: The Microbiome and Inflammatory Bowel Diseasementioning

confidence: 99%

The microbiome and inflammatory bowel disease

Glassner

Abraham

Quigley

2020

Journal of Allergy and Clinical Immunology

600

363

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Inflammatory bowel disease (IBD) is a chronic immunemediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiotamodulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies. (J

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Section: The Microbiome and Inflammatory Bowel Diseasementioning

confidence: 99%

The microbiome and inflammatory bowel disease

Glassner

Abraham

Quigley

2020

Journal of Allergy and Clinical Immunology

600

363

View full text Add to dashboard Cite

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“…A plausible model for the development of CD is that alteration of the gut microbiota through an acute event, such as an infectious gastroenteritis or the use of broad-spectrum antibiotics, creates a niche for AIEC proliferation. The potentiation of acute infectious gastroenteritis in mice previously colonised with AIEC can lead to the expansion of tissue-associated AIEC and a chronic intestinal inflammatory response with subsequent bowel damage 155. These findings suggest that individuals colonised by AIEC at the time of acute gastroenteritis may be at a greater risk for CD development 155…”

Section: Aiec In Ibdmentioning

confidence: 99%

Adherent-invasive Escherichia coli in inflammatory bowel disease

Palmela

Chevarin

et al. 2017

Gut

405

318

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Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn’s disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.

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“…In fact, AIEC have been shown to facilitate a response to a flare in IBD patients and ability of an IBD-susceptible host to recover from an 'event' such as acute colitis caused by ingestion of a foodborne pathogen thus potentiating IBD progression (Mirsepasi-Lauridsen et al, 2019). Of note, mice infected with mAIEC fail to recover (body weight loss and increased disease activity) from DSS-induced colitis (Small et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The Autoimmune Susceptibility Gene, PTPN2, Restricts Expansion of a Novel Mouse Adherent-Invasive E. coli

Shawki

Alvarez

Spalinger

et al. 2019

Preprint

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Inflammatory bowel diseases (IBD) involve genetic and environmental factors that play major roles in disease pathogenesis. Loss-of-function single-nucleotide polymorphisms (SNPs) in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene increase the risk of IBD and are associated with altered microbiome population dynamics in IBD. Moreover, expansion of intestinal pathobionts, such as adherent-invasive E. coli (AIEC), is strongly implicated in the pathogenesis of IBD as AIEC increases pro-inflammatory cytokine production and alters tight junction protein regulation suggesting a potential mechanism of pathogen-induced barrier dysfunction and inflammation. The aim of this study was to identify if PTPN2 deficiency disturbs the composition of the intestinal microbiome to promote expansion of specific bacteria with pathogenic properties. In mice constitutively lacking Ptpn2 we identified increased abundance of a novel adherent-invasive E. coli (AIEC) that showed similar adherence and invasion of intestinal epithelial cells, but greater survival in macrophages to the IBD associated AIEC, LF82. Furthermore, we confirmed this novel mouse AIEC (mAIEC) caused disease when administered to germ-free and mice lacking segmented-filamentous bacteria (SFB). Moreover, mAIEC infection increased severity of and prevented recovery from dextran-sodium sulfate (DSS)induced colitis. mAIEC genome sequence analysis showed >90% similarity to LF82. Interestingly, mAIEC contained distinct attachment genes not found in LF82 thereby also demonstrating the novelty of this AIEC. We show here for the first time that an IBD susceptibility gene, PTPN2, plays a key role in modulating the gut microbiome to protect against a novel pathobiont. This study generates new insights into gene-environment-microbiome interactions in IBD.

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Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period

Cited by 38 publications

References 53 publications

The microbiome and inflammatory bowel disease

The microbiome and inflammatory bowel disease

Adherent-invasive Escherichia coli in inflammatory bowel disease

The Autoimmune Susceptibility Gene, PTPN2, Restricts Expansion of a Novel Mouse Adherent-Invasive E. coli

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