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.
Purpose of Review
Diagnosis of autoimmune gastritis (AIG) is often delayed because of the absence of typical symptoms. Clinical guidelines are lacking which results in inadequate treatment and poor cancer screening. This review presents an overview of current management options and aims at raising awareness for this often-neglected disease.
Recent Findings
Autoimmune gastritis is mostly thought of as a disease of the elderly with vitamin B12 deficiency and pernicious anemia. Today it is recognized that AIG is found with a similar prevalence among all age-groups, with iron deficiency being a frequent feature. Conventional therapy consists of adequate iron and vitamin B12 supplementation as well as symptomatic approaches. The associated risk for gastric adenocarcinoma and gastric neuroendocrine tumors requires regular endoscopic follow up. Novel therapies aiming to reduce gastric atrophy and cancer risk are currently under development.
Summary
Treatment of autoimmune gastritis should focus on optimizing supplementation of deficiencies and include cancer prevention measures. Clinical research should address the possibility to arrest the inflammatory process and to prevent progression of AIG. International guidelines on management and endoscopic screening intervals should be set up.
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