Intestinal Barrier in Post-Campylobacter jejuni Irritable Bowel Syndrome

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Abstract

Background: Campylobacter jejuni (C. jejuni) is one of the most common causes of bacterial gastroenteritis worldwide. One sequela of this infection is the development of post-infectious irritable bowel syndrome (PI-IBS). It has been suggested that a dysfunctional intestinal barrier may promote IBS development. We aimed to test this hypothesis against the background of the leaky gut concept for low-grade inflammation in PI-IBS. Methods: We identified patients with persistent PI-IBS symptoms after C. jejuni infection. During sigmoidoscopy, forceps biopsies were obtained for electrophysiological measurements of epithelial transport and barrier function in miniaturized Ussing devices. C. jejuni absence was checked by PCR and cytokine production with immunohistochemistry. Results: In PI-IBS, the epithelial resistance of the colon epithelium was unaltered, reflecting an intact paracellular pathway. In contrast, temperature-dependent horseradish peroxidase (HRP, 44 kDa) permeation increased. Short-circuit current (Isc) reflecting active anion secretion and ENaC-dependent electrogenic sodium absorption was unaffected. Early endosome antigen-1 (EEA1) and IL-4 levels increased. C. jejuni is not incorporated into the resident microbiota of the colon mucosa in PI-IBS. Conclusions: In PI-IBS after C. jejuni infection, macromolecule uptake via endocytosis was enhanced, leading to low-grade inflammation with pro-inflammatory cytokine release. The findings will allow C. jejuni-induced pathomechanisms to be targeted during infection and, thereafter to reduce sequelae such as PI-IBS.

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Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis.

Rebecca M. Lovell, Alexander Ford (2012)

Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Global Epidemiology of Campylobacter Infection.

Nadeem Kaakoush, Natalia Castaño-Rodríguez, Hazel M. Mitchell … (2015)

Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.

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Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways

Nicholas Bellono, James Bayrer, Duncan B. Leitch … (2017)

Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principle site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotoninsensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system. Use of organoids to characterize rare chemosensory cells in the gut elucidated their biophysical, pharmacological and genetic properties, and showed that they communicate directly with neural sensory pathways.