Atypical enteropathogenic E. coli are associated with disease activity in ulcerative colitis

Abstract

With increasing urbanization and industrialization, the prevalence of inflammatory bowel diseases (IBDs) has steadily been rising over the past two decades. IBD involves flares of gastrointestinal (GI) inflammation accompanied by microbiota perturbations. However, microbial mechanisms that trigger such flares remain elusive. Here, we analyzed the association of the emerging pathogen atypical enteropathogenic E. coli (aEPEC) with IBD disease activity. The presence of diarrheagenic E. coli was assessed in stool samples from 630 IBD patients and 234 age- and sex-matched controls without GI symptoms. Microbiota was analyzed with 16S ribosomal RNA gene amplicon sequencing, and 57 clinical aEPEC isolates were subjected to whole-genome sequencing and in vitro pathogenicity experiments including biofilm formation, epithelial barrier function and the ability to induce pro-inflammatory signaling. The presence of aEPEC correlated with laboratory, clinical and endoscopic disease activity in ulcerative colitis (UC), as well as microbiota dysbiosis. In vitro, aEPEC strains induce epithelial p21-activated kinases, disrupt the epithelial barrier and display potent biofilm formation. The effector proteins espV and espG2 distinguish aEPEC cultured from UC and Crohn’s disease patients, respectively. EspV-positive aEPEC harbor more virulence factors and have a higher pro-inflammatory potential, which is counteracted by 5-ASA. aEPEC may tip a fragile immune–microbiota homeostasis and thereby contribute to flares in UC. aEPEC isolates from UC patients display properties to disrupt the epithelial barrier and to induce pro-inflammatory signaling in vitro.

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

“…Similarly, metagenomics sequencing of gut microbes also demonstrated that the microbial diversity in IBD patients is obviously attenuated compared to that in healthy individuals, especially beneficial bacteria, such as Bacteroides , Lactobacillus , and Eubacterium , causing oxidative stress and leading to gut dysbiosis and inflammation [ 66 , 67 ]. In parallel, some incremental pathogenic bacteria, such as adherent invasive Escherichia coli ( E. coli ) [ 68 ], can lead to damage to the intestinal mucosal epithelium and enhance intestinal permeability, causing gut metabolic wastes (e.g., cadaverine, taurine) and bacterial metabolic toxins, such as lipopolysaccharide (LPS), to permeate into the blood and eventually aggravating IBD [ 69 , 70 , 71 ]. In summary, therapeutic strategies that restore gut microbiota homeostasis by regulating the ratio of beneficial bacteria to pathogenic bacteria and relieving oxidative stress and inflammation have great promise.…”

Impressive pan-genomic diversity of E. coli from a wild animal community near urban development reflects human impacts

“…No isolates were positive for the gene bfpA (bundle-forming pilus), so those containing the gene coding for the enteropathogenic E. coli -associated intimin protein, eae, were considered atypical; aEPEC. 38 Of the wild hosts, at least one pathogen was obtained from 65.3% of individuals, as well as the squirrel midden and bat roost. Of the domestic hosts, a pathogen was found in 18.2% of individuals (just 2 horses), and the goat herd.…”

Correlation between microbial characteristics and reproductive status of the yak uterus based on macrogenomic analysis

“…Additionally, patients with colorectal cancer have an increased abundance of baiP and baiJ in B. subtilis compared to healthy individuals [ 36 ]. Atypical enteropathogenic E. coli can also disrupt the stability of immune microbiota and cause ulcerative colitis [ 37 ]. Therefore, exploring the diversity of the uterine microbiota in animals in different reproductive stages is important for analyzing the correlation between the microbiota and reproductive regulation.…”