Escherichia coli in chronic inflammatory bowel diseases: An update on adherent invasive Escherichia coli pathogenicity

Escherichia coli(E. coli), and particularly the adherent invasive E. coli(AIEC) pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn's disease(CD). E. coli strains with similar pathogenic features to AIEC have been associated with other intestinal disorders such as ulcerative colitis, colorectal cancer, and coeliac disease, but AIEC prevalence in these diseases remains largely unexplored. Since AIEC was described one decade ago, substantial progress has been made in deciphering its mechanisms of pathogenicity. However, the molecular bases that characterize the phenotypic properties of this pathotype are still not well resolved. A review of studies focused on E. coli populations in inflammatory bowel disease(IBD) is presented here and we discuss about the putative role of this species on each IBD subtype. Given the relevance of AIEC in CD pathogenesis, we present the latest research findings concerning AIEC host-microbe interactions and pathogenicity. We also review the existing data regarding the prevalence and abundance of AIEC in CD and its association with other intestinal diseases from humans and animals, in order to discuss the AIEC disease- and hostspecificity. Finally, we highlight the fact that dietarycomponents frequently found in industrialized countries may enhance AIEC colonization in the gut, which merits further investigation and the implementation of preventative measures.

Why the discovery of adherent-invasive Escherichia coli molecular markers is so challenging?

Adherent-invasive Escherichia coli(AIEC)strains have been extensively related to Crohn’s disease(CD)etiopathogenesis.Higher AIEC prevalence in CD patients versus controls has been reported,and its mechanisms of pathogenicity have been linked to CD physiopathology.In CD,the therapeutic armamentarium remains limited and non-curative;hence,the necessity to better understand AIEC as a putative instigator or propagator of the disease is certain.Nonetheless,AIEC identification is currently challenging because it relies on phenotypic assays based on infected cell cultures which are highly time-consuming,laborious and non-standardizable.To address this issue,AIEC molecular mechanisms and virulence genes have been studied;however,a specific and widely distributed genetic AIEC marker is still missing.The finding of molecular tools to easily identify AIEC could be useful in the identification of AIEC carriers who could profit from personalized treatment.Also,it would significantly promote AIEC epidemiological studies.Here,we reviewed the existing data regarding AIEC genetics and presented those molecular markers that could assist with AIEC identification.Finally,we highlighted the problems behind the discovery of exclusive AIEC biomarkers and proposed strategies to facilitate the search of AIEC signature sequences.

Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification

BACKGROUND The challenges for inflammatory bowel disease(IBD)diagnostics are to discriminate it from gut conditions with similar symptoms such as irritable bowel syndrome(IBS),to distinguish IBD subtypes,to predict disease progression,and to establish the risk to develop colorectal cancer(CRC).Alterations in gut microbiota have been proposed as a source of information to assist in IBD diagnostics.Faecalibacterium prausnitzii(F.prausnitzii),its phylogroups,and Escherichia coli(E.coli)have been reported as potential biomarkers,but their performance in challenging IBD diagnostic situations remains elusive.We hypothesize that bacterial biomarkers based in these species may help to discriminate these conditions of complex diagnostics.AIM To evaluate the usefulness of indices calculated from the quantification of these species as biomarkers to aid in IBD diagnostics.METHODS A retrospective study of 131 subjects(31 controls(H);45 Crohn’s disease(CD),25 ulcerative colitis(UC),10 IBS,and 20 CRC patients)was performed to assess the usefulness of bacterial biomarkers in biopsies.Further,the performance of biomarkers in faeces was studied in 29 stool samples(19 CD,10 UC).Relative abundances of total F.prausnitzii(FP),its phylogroups(PHGI and PHGII),and E.coli(E)quantification were determined by qPCR.Loads were combined to calculate the FP-E index,the PHGI–E index and the PHGII-E index.Biomarkers accuracy to discriminate among conditions was measured by the area under the receiver operating characteristic curve(AUC).RESULTS In biopsies,FP-E index was good for discriminating IBS from CD(AUC=0.752)while PHGII-E index was suitable for discriminating IBS from UC(AUC=0.632).The FP-E index would be the choice to discriminate IBD from CRC,especially from all UC subtypes(AUC≥0.875),regardless of the activity status of the patient.Discrimination between UC patients that had the longest disease duration and those with CRC featured slightly lower AUC values.Concerning differentiation in IBD with shared location,PHGI-E index can establish progression from proctitis and left-sided colitis to ulcerative pancolitis(AUC≥0.800).PHG I-E index analysis in tissue would be the choice to discriminate within IBD subtypes of shared location(AUC≥0.712),while in non-invasive faecal samples FP or PHGI could be good indicators(AUC≥0.833).CONCLUSION F.prausnitzii phylogroups combined with E.coli offer potential to discriminate between IBD and CRC patients and can assist in IBD subtypes classification,which may help in solving IBD diagnostics challenges.