Distinct inflammatory and cytopathic characteristics of Escherichia coli isolates from inflammatory bowel disease patients

Abstract

Escherichia coli (E. coli) may be implicated in the pathogenesis of inflammatory bowel disease (IBD), as implied from a higher prevalence of mucosa-associated E. coli in the gut of IBD-affected individuals. However, it is unclear whether different non-diarrheagenic E. coli spp. segregate from each other in their ability to promote intestinal inflammation. Herein we compared the inflammation-inducing properties of non-diarrheagenic LF82, 691-04A, E. coli Nissle 1917 (ECN) and eleven new intestinal isolates from different locations in five IBD patients and one healthy control. Viable E. coli were cultured with human monocyte-derived dendritic cells (moDCs) and monolayers of intestinal epithelial cells (IECs), followed by analysis of secreted cytokines, intracellular levels of reactive oxygen species and cellular death. The IBD-associated E. coli LF82 induced the same dose-dependent inflammatory cytokine profile as ECN and ten of the new E. coli isolates displayed as high level IL-12p70, IL-1β, IL-23 and TNF-α from moDCs irrespective of their site of isolation (ileum/colon/faeces), disease origin (diseased/non-diseased) or known virulence factors. Contrarily, 691-04A and one new IBD E. coli isolate induced a different cellular phenotype with enhanced killing of moDCs and IECs, coupled to elevated IL-18. The cytopathic nature of 691-04A and one other IBD E. coli isolate suggests that colonization with specific non-diarrheagenic E. coli could promote intestinal barrier leakage and profound intestinal inflammation, while LF82, ECN and the remaining non-diarrheagenic E. coli isolates hold notorious pro-inflammatory characteristics that can progress inflammation in case of intestinal barrier leakage.

Escherichia coli Pathobionts Associated with Inflammatory Bowel Disease

“…The potential causal role of IBD-associated E. coli in the pathophysiology of IBD has been linked to the ability to adhere to and invade epithelial cells and multiply within macrophages, such as that seen with the prototypical AIEC strain, LF82. Our studies have shown that UC-associated E. coli (p19A) from the B2 phylogenetic group (ExPEC), harboring two alpha-hemolysin genes, induces cell death in dendritic cells, stimulates the release of the cytokines TNF-␣, IL-6, and IL-23 (99), and causes rapid loss of the TJ integrity in differentiated Caco2-cell monolayers (38). The difference between p19A and strain LF82 is that LF82 does not disturb the epithelial TJ, obviously indicating that these two IBD-associated strains, both from the B2 phylogenetic group, differ in their pathogenic mechanisms.…”

“…Mirsepasi-Lauridsen et al (38) showed that UC-associated E. coli p19A, an ExPEC strain harboring alpha-hemolysin, dissolved the TJ protein occludin in cell lines and disrupted the TJ in Caco-2 cells in vitro, followed by increasing barrier permeability (38). Additionally, the UC-associated E. coli strain p19A induces cell death in dendritic cells and stimulates the release of the cytokines TNF-␣, IL-6, and IL-23 (99). As is the case with AIEC and CD, the link between DAEC and/or B2 E. coli is associative, and no data so far reveal a causative link.…”

Fecal Enterobacteriales enrichment is associated with increased in vivo intestinal permeability in humans

“…coli in disease pathogenesis remains uncertain (Jensen et al. ; Matsuoka and Kanai ; König et al. ).…”

“…Nonetheless, Proteobacteria and E. coli enrichment has also been observed in patients with inflammatory bowel disease which is associated with increased intestinal permeability. The role of Proteobacteria and E. coli in disease pathogenesis remains uncertain (Jensen et al 2015;Matsuoka and Kanai 2015;K€ onig et al 2016). However, Enterobacteriaceae enrichment has been observed in other clinical scenarios, such as following gastric bypass surgery (RYGB), with no detrimental effects to the host.…”

Interleukin-8, CXCL1, and MicroRNA miR-146a Responses to Probiotic Escherichia coli Nissle 1917 and Enteropathogenic E. coli in Human Intestinal Epithelial T84 and Monocytic THP-1 Cells after Apical or Basolateral Infection

“…Neutrophil infiltration is classically associated with an increase in IBD activity and an increase in inflammation (50). Moreover, in acute inflammatory bowel disease, where a compromised intestinal barrier is very likely, basolateral access of microbes, including commensals and probiotics introduced for therapy, is possible and may result in progressive inflammation (51). In contrast, however, there is a growing number of reports that emphasize beneficial effects of neutrophil infiltration (52).…”