Abstract:Crohn’s disease (CD) is a multifactorial pathology associated with the presence of adherent-invasive Escherichia coli (AIEC) and NLRP3 polymorphic variants. The presence of intracellular E. coli in other intestinal pathologies (OIP) and the role of NLRP3-inflammasome in the immune response activated by these bacteria have not been investigated. In this study, we sought to characterize intracellular strains isolated from patients with CD, ulcerative colitis (UC) and OIP, and analyze NLRP3-inflammasome role in t… Show more
“…Our results further support the idea that AIEC might have more than one mechanism to interact with M cells and access the underlying macrophages present in the lymphoid tissue. The survival within murine macrophages by AIEC isolates has been well described (3), where the survival at 24 h postinfection can range from 32 to 100% of bacteria phagocytosed in the case of the Crohn's disease-associated strains (4,51). In our study, the survival of NRG857c in human macrophages at 24 h postinfection was 32.42%, which is consistent with what has been reported for other AIEC strains.…”
“…Our results further support the idea that AIEC might have more than one mechanism to interact with M cells and access the underlying macrophages present in the lymphoid tissue. The survival within murine macrophages by AIEC isolates has been well described (3), where the survival at 24 h postinfection can range from 32 to 100% of bacteria phagocytosed in the case of the Crohn's disease-associated strains (4,51). In our study, the survival of NRG857c in human macrophages at 24 h postinfection was 32.42%, which is consistent with what has been reported for other AIEC strains.…”
“…The qPCR results suggested that this increase was due to E. coli, and this group is of particular interest, as previous studies have reported an increased virulent potential of E. coli, such as adhesive capacity, invasive capacity, toxin production, and inflammatory cytokine stimulation, in human patients with IBD. 29,30 Adherent and invasive E. coli strains have been reported specifically in Boxer dogs with granulomatous colitis. 31 Whether the virulent potential of E. coli plays a similar role in other forms of canine inflammatory bowel disease remains to be determined.…”
Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the hostmicrobe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n D 10) and dogs with IBD before and after 3 weeks of medical therapy (n D 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.
“…AIEC survival and replication in macrophages is promoted by the stress protein HtrA,67 the thiol-disulfide oxidoreductase DsbA,68 the RNA-binding protein Hfq69 and the FAD-dependent oxydoreductase IbeA70 that play a role in surviving reactive oxygen species (ROS) (table 1). In response to AIEC infection, tumour necrosis factor α (TNF-α)35 71 72 and other proinflammatory cytokines73 are released, further enhancing dysbiosis and proliferation of AIEC without inducing host cell death. AIEC are able to exploit host mechanisms of apoptosis by increasing S-nitrosylation and proteasomal degradation of caspase-3 in infected macrophages,74favouring their own intracellular replication through modulation of the ubiquitin proteasome system in infected-IEC,75 76 and through the release of exosomes from infected cells 77.…”
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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