Phage Therapy Against Adherent-invasive <i>E. coli</i>: Towards a Promising Treatment of Crohn’s Disease Patients?

Boucher, Delphine; Barnich, Nicolas

doi:10.1093/ecco-jcc/jjac070

Cited by 6 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phage therapy has been explored as a promising tool for the eradication of AIEC in CD [69]. Moreover, phage therapy against AIEC in CD patients was found to be safe and effective [70].…”

Section: -Phage Therapymentioning

confidence: 99%

Antibiotic Therapy for Active Crohn’s Disease Targeting Pathogens: An Overview and Update

Iaquinto,

Mazzarella,

Sellitto

et al. 2024

Antibiotics

View full text Add to dashboard Cite

Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors, including genetics, immune response, and gut microbiota. Therapy includes salicylates, immunosuppressive agents, corticosteroids, and biologic drugs. International guidelines do not recommend the use of antibiotics for CD patients, except in the case of septic complications. Increasing evidence of the involvement of gut bacteria in this chronic disease supports the rationale for using antibiotics as the primary treatment for active CD. In recent decades, several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E. coli) and Mycobacterium avium paratubercolosis (MAP) have aroused interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment for CD patients, but randomized trials testing antibiotic treatment against E. coli and MAP have not shown prolonged benefits and have generated conflicting results; several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course, and the outcome measures. In this paper, we provide an overview and update of the trials testing antibiotic treatment for active CD patients, taking into account the role of pathogens, the mechanisms by which different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also present new lines of study for the future regarding the use of antibiotics to treat patients with active CD.

show abstract

“…Phage therapy has been explored as a promising tool for the eradication of AIEC in CD [69]. Moreover, phage therapy against AIEC in CD patients was found to be safe and effective [70].…”

Section: -Phage Therapymentioning

confidence: 99%

Antibiotic Therapy for Active Crohn’s Disease Targeting Pathogens: An Overview and Update

Iaquinto,

Mazzarella,

Sellitto

et al. 2024

Antibiotics

View full text Add to dashboard Cite

show abstract

“…For this reason, before considering a clinical application in ileal CD, further studies are needed to prevent possible adverse effects induced by the modulation of these epigenetic targets or to identify more specific genes associated with AIEC colonisation. Another promising approach would be the use of bacteriophages to target specifically AIEC in ileal disease[ 111 ]. To date, no bacteriophage has been approved for intestinal therapeutic use in human, either in the European Union or in the United States, despite numerous studies that have reported encouraging results in vivo.…”

Section: Microbiotamentioning

confidence: 99%

“…To date, no bacteriophage has been approved for intestinal therapeutic use in human, either in the European Union or in the United States, despite numerous studies that have reported encouraging results in vivo. Therefore, data about the effect of bacteriophages on human microbiota are needed in the future[ 111 ].…”

Section: Microbiotamentioning

confidence: 99%

Crohn’s disease: Why the ileum?

Richard¹,

Savoye²,

Leboutte³

et al. 2023

World J Gastroenterol

View full text Add to dashboard Cite

Crohn’s disease (CD) is an inflammatory bowel disease characterized by immune-mediated flares affecting any region of the intestine alternating with remission periods. In CD, the ileum is frequently affected and about one third of patients presents with a pure ileal type. Moreover, the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes. Most of these genes are associated with Paneth cell dysfunction, a cell type found in the intestinal crypts of the ileum. Besides, a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota, which in turn modulates the susceptibility of the ileum to inflammation. Thus, the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis. Indeed, both immune response and cellular healing processes harbour differences between ileal and non-ileal CD. Taken together, these findings advocate for a dedicated therapeutic approach to managing ileal CD. Currently, interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site. However, the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.

show abstract

“…A hall mark of AIEC infection is replication to high levels within infected macrophages, where it can stall cell death pathways, a likely contributory factor in granuloma formation (Meconi et al ., 2007; Dunne et al ., 2013). With a paucity of information regarding the key drivers for the success of infection in the host-pathogen relationship, the treatment of AIEC infection in the context of CD has proved challenging, although recent progress has been made (Boucher and Barnich, 2022; Douadi et al ., 2022; Gerner et al ., 2022; Titécat et al ., 2022). However, while AIEC replicates and persists to high levels in some infected macrophages this does not occur in all infected cells.…”

Section: Introductionmentioning

confidence: 99%

Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn’s disease associated adherent-invasiveEscherichia coliinfection

Li,

Cole,

Vaughan

et al. 2024

Preprint

View full text Add to dashboard Cite

Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their bacterial load and duration of infection. In the case of infection of macrophages with Crohn’s disease (CD) associated adherent-invasiveEscherichia coli(AIEC), understanding the drivers of pathogen success may allow targeting of cells where AIEC replicate to high levels. Here we show that stratifying immune cells based on their bacterial load identifies novel pathways and therapeutic targets not previously associated with AIEC when using a traditional homogeneous infected population approach. Using flow cytometry-based cell sorting we stratified cells into those with low or high intracellular pathogen loads, or those which were bystanders to infection. Immune cells transcriptomics revealed a diverse response to the varying levels of infection while pathway analysis identified novel intervention targets that were directly related to increasing intracellular AIEC numbers. Chemical inhibition of identified targets reduced AIEC intracellular replication or inhibited secretion of tumour necrosis factor alpha (TNFα), a key cytokine associated with AIEC infection. Our results have identified new avenues of intervention in AIEC infection that may also be applicable to CD through the repurposing of already available inhibitors. Additionally, they highlight the applicability of immune cell stratification post-infection as an effective approach for the study of microbial pathogens.

show abstract

Phage Therapy Against Adherent-invasive E. coli: Towards a Promising Treatment of Crohn’s Disease Patients?

Cited by 6 publications

References 10 publications

Antibiotic Therapy for Active Crohn’s Disease Targeting Pathogens: An Overview and Update

Antibiotic Therapy for Active Crohn’s Disease Targeting Pathogens: An Overview and Update

Crohn’s disease: Why the ileum?

Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn’s disease associated adherent-invasiveEscherichia coliinfection

Contact Info

Product

Resources

About