AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation

Bretin, Alexis; Lucas, Cécily; Larabi, Anaïs; Dalmasso, Guillaume; Billard, Elisabeth; Barnich, Nicolas; Bonnet, Richard; Nguyen, Hang Thi Thu

doi:10.1038/s41598-018-30055-y

Cited by 56 publications

(46 citation statements)

References 54 publications

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“…108 Bretin and colleagues recently suggested that transient AIEC infection in mice can promote inflammatory signaling after clearance of the pathobiont. 136 These data demonstrate that pathobionts are able to induce stress responses and inflammatory signaling in IECs and may continue to promote inflammation long after infection.…”

Section: Activation Of Immune and Stress Responsesmentioning

confidence: 76%

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Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

King

McCole

2019

Intest Res

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Inflammatory bowel diseases (IBD) are chronic conditions of the gastrointestinal tract-the main site of host-microbial interaction in the body. Development of IBD is not due to a single event but rather is a multifactorial process where a patient’s genetic background, behavioral habits, and environmental exposures contribute to disease pathogenesis. IBD patients exhibit alterations to gut bacterial populations “dysbiosis” due to the inflammatory microenvironment, however whether this alteration of the gut microbiota precedes inflammation has not been confirmed. Emerging evidence has highlighted the important role of gut microbes in developing measured immune responses and modulating other host responses such as metabolism. Much of the work on the gut microbiota has been correlative and there is an increasing need to understand the intimate relationship between host and microbe. In this review, we highlight how commensal and pathogenic bacteria interact with host intestinal epithelial cells and explore how altered microenvironments impact these connections.

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Section: Activation Of Immune and Stress Responsesmentioning

confidence: 76%

“…For example, Helicobacter bilis does not alter microbial composition while adherent-invasive E. coli induces dysbiosis despite commensal-directed immune responses. 135,136 In this section we review the current understanding of various pathobionts in the GI tract.…”

Section: Pathobiont Bacteria and Intestinal Function In Ibdmentioning

confidence: 99%

Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

King

McCole

2019

Intest Res

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“…Recently, our group showed that deficiency of the amino acid deprivation sensor EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4) in mice, which leads to impaired autophagy-mediated clearance of CD-associated AIEC and consequently enhanced inflammation [29], induces changes in the fecal microbiota composition upon AIEC colonization but not under the steady state [30]. This suggested that in some conditions, defective autophagy alone does not trigger intestinal dysbiosis but its combination with an infectious agent can do so.…”

Section: Autophagy and Gut Microbiotamentioning

confidence: 99%

New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

2019

Self Cite

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One of the most significant challenges of inflammatory bowel disease (IBD) research is to understand how alterations in the symbiotic relationship between the genetic composition of the host and the intestinal microbiota, under impact of specific environmental factors, lead to chronic intestinal inflammation. Genome-wide association studies, followed by functional studies, have identified a role for numerous autophagy genes in IBD, especially in Crohn disease. Studies using in vitro and in vivo models, in addition to human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis maintenance, gut ecology regulation, appropriate intestinal immune responses and anti-microbial protection. This review describes the latest researches on the mechanisms by which dysfunctional autophagy leads to disrupted intestinal epithelial function, gut dysbiosis, defect in anti-microbial peptide secretion by Paneth cells, endoplasmic reticulum stress response and aberrant immune responses to pathogenic bacteria. A better understanding of the role of autophagy in IBD pathogenesis may provide better sub-classification of IBD phenotypes and novel approaches for disease management.

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“…First, by "spiking in" the EAEC strain into the fecal culture, the a-diversity is of course altered (Fig. 5), not unlike when humans are infected with enteric pathogens, and this has also been demonstrated in mice (62). In contrast, the gut microbiome a-diversity was observed to be reduced up to 40% in patients given ciprofloxacin, a fluoroquinolone commonly prescribed for E. coli infections (16).…”

Section: Discussionmentioning

confidence: 94%

MyoviridaePhagePDXKills EnteroaggregativeEscherichia coliwithout Human Microbiome Dysbiosis

Cepko

Garling

Dinsdale

et al. 2018

Preprint

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Escherichia virus, microbiome, dysbiosis antibiotic alternatives. AbstractPurpose. To identify therapeutic a bacteriophage that kills diarrheagenic enteroaggregative Escherichia coli (EAEC) while leaving the human microbiome intact.Methodology. Phages from wastewater in Portland, OR, were screened for bacteriolytic activity using an overlay assay, and isolated in a sequential procedure to enrich for the recognition of core bacterial antigens. Electron microscopy and genome sequencing were performed to classify the isolated phage, and the host range was determined by spot tests and plaque assays. One-step growth curves and time-kill assays were conducted to characterize the life cycle of the phage, and to interrogate the multiplicity of infection (MOI) necessary for killing. A mouse model of infection was used to determine whether the phage could be used therapeutically against EAEC in vivo. Anaerobic culture in the presence of human fecal bacteria determined whether the phage could kill EAEC in vitro, and to assess whether the microbiome had been altered.Results. The isolated phage, termed Escherichia virus PDX, is a member of the strictly lytic Myoviridae family of viruses. Phage PDX killed EAEC isolate EN1E-0227, a case-associated isolate from a child in rural Tennessee, in a dose-dependent manner, and also formed plaques on case-associated clinical EAEC isolates from Columbian children suffering from diarrhea. A single dose of PDX, at a MOI of 100, one day post infection, reduced the population of recovered EAEC isolate EN1E-0227 bacteria in fecal pellets in a mouse model of colonization, over a fiveday period. Phage PDX also killed EAEC EN1E-0227 when cultured anaerobically in vitro in the presence of human fecal bacteria. While the addition of EAEC EN1E-0227 reduced the adiversity of the human microbiota, that of the cultures with either feces alone, feces with EAEC and PDX, or with just the PDX phage were not different statistically, as measured by Chao1 and Shannon diversity indices. Additionally, b-diversity and differential abundance analyses show that conditions with PDX added were not different from feces alone, but all groups were significantly different from feces + EAEC.Conclusions. The strictly bacteriolytic, Myoviridae Escherichia virus PDX killed EAEC isolate EN1E-0227 bacteria both in vivo and in vitro, while simultaneously not altering the diversity of normal human microbiota in anaerobic culture. Thus, the PDX phage could be part of an effective therapeutic intervention for children in developing countries who suffer from acute, or persistent EAEC-mediated diarrhea, and to help reduce the serious effects of environmental enteropathy. Because the emerging pathogen EAEC is now the second leading cause of traveler's diarrhea, PDX could also provide therapeutic relief for these individuals, particularly in light of the growing crisis of antibiotic resistances.

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AIEC infection triggers modification of gut microbiota composition in genetically predisposed mice, contributing to intestinal inflammation

Cited by 56 publications

References 54 publications

Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

MyoviridaePhagePDXKills EnteroaggregativeEscherichia coliwithout Human Microbiome Dysbiosis

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