Effect of genetic background and postinfectious stress on visceral sensitivity in <i>Citrobacter rodentium</i>‐infected mice

Mondelaers, Stéphanie; Theofanous, Stavroula; Florens, Morgane; Perna, Eluisa; Aguilera‐Lizarraga, Javier; Boeckxstaens, Guy E.; Wouters, Mira M.

doi:10.1111/nmo.12759

Cited by 17 publications

(19 citation statements)

References 65 publications

(114 reference statements)

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“…The visceromotor response (VMR) was measured and quantified using Ponemah Software System (Ponemah Software 5.20, Ponemah Core Software Configured with MX2 4 Source Acquisition Interface, Electromyogram Analysis Software Module). For analysis, the mean value of the resting EMG signal 10 second prior to distension (ie, basal activity) was subtracted from the mean value of the electromyography signal evoked during the 10‐second distension …”

Section: Methodsmentioning

confidence: 99%

Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

Theofanous

Florens

Appeltans

et al. 2020

Neurogastroenterology Motil

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Background Ephrin‐B2/EphB receptor signaling contributes to persistent pain states such as postinflammatory and neuropathic pain. Visceral hypersensitivity (VHS) is a major mechanism underlying abdominal pain in patients with irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) in remission, but the underlying pathophysiology remains unclear. Here, we evaluated the spinal ephrin‐B2/EphB pathway in VHS in 2 murine models of VHS, that is, postinflammatory TNBS colitis and maternal separation (MS). Methods Wild‐type (WT) mice and mice lacking ephrin‐B2 in Nav1.8 nociceptive neurons (cKO) were studied. VHS was induced by: 1. intracolonic instillation of TNBS or 2. water avoidance stress (WAS) in mice that underwent maternal separation (MS). VHS was assessed by quantifying the visceromotor response (VMRs) during colorectal distention. Colonic tissue and spinal cord were collected for histology, gene, and protein expression evaluation. Key Results In WT mice, but not cKO mice, TNBS induced VHS at day 14 after instillation, which returned to baseline perception from day 28 onwards. In MS WT mice, WAS induced VHS for up to 4 weeks. In cKO however, visceral pain perception returned to basal level by week 4. The development of VHS in WT mice was associated with significant upregulation of spinal ephrin‐B2 and EphB1 mRNA expression or protein levels in the TNBS model and upregulation of spinal ephrin‐B2 protein in the MS model. No changes were observed in cKO mice. VHS was not associated with persistent intestinal inflammation. Conclusions and Inferences Overall, our data indicate that the ephrin‐B2/EphB1 spinal signaling pathway is involved in VHS and may represent a novel therapeutic target.

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Section: Methodsmentioning

confidence: 99%

Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

Theofanous

Florens

Appeltans

et al. 2020

Neurogastroenterology Motil

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“…Long-lasting effects of Cr infection seems to be dependent on genetic predisposition, as Th-2 predominant BALB/c mice maintained visceral hypersensitivity for longer period of time than Th-1 predominant C57Bl/6 mice. 94 The advantages of this model are the use of a bacterial pathogen that closely resembles that involved in PI-IBS, and development of hyperalgesia but no changes in motility or permeability were shown so far.…”

Section: Animal Modelsmentioning

confidence: 99%

Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome

et al. 2019

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Background & Aims The existence of post-infection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report was to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based upon findings reported in the literature and clinical experience. Methods The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. Results PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or prior to acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There is no evidence- based effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. Conclusions Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based upon team consensus. We also propose areas for investigations.

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“…Sample collection time could be one reason for the reduced number of differentially expressed cytokines, as a number of studies have reported that the peak response (IL-17a, IL-17f, IL-22, IL-1β, TNF, and IFN-γ) is between 8 and 21 (Lupp et al, 2007;Hoffmann et al, 2009;Mondelaers et al, 2016) days post-dosing.…”

Section: Effect Of Adr-159 On Citrobacter-induced Colitismentioning

confidence: 99%

Oral Administration of Heat-Treated Lactobacilli Modifies the Murine Microbiome and Reduces Citrobacter Induced Colitis

et al. 2020

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Significant evidence supports a relationship between the gut microbiome, inflammation, host response, and health, including the finding that a number of disorders are associated with disruption of the microbiome. In these disorders, a number of dietary interventions (including prebiotics, live probiotics, or heat-killed microbes) have been proposed to be curative or preventative agents. The use of heat-killed microbes has a number of benefits over living organisms, including reduced infection risk in vulnerable individuals, extended shelf life and the potential for use in combination with antimicrobial agents. We previously reported that murine chow supplemented with 5% ADR-159, a heat-treated fermentate generated by two Lactobacillus strains, altered both behavior and the microbiome of male mice. Now we show that ADR-159 fed female mice also display a similar microbiome shift as determined by 16S rDNA analysis. In particular, we observed a reduction of levels of Turicibacter and Clostridium sensu stricto. These subtle changes in the bacterial component of the microbiome were mirrored by changes in the virome. Extended consumption of the ADR-159 diet had no negative effect on general health and lipocalin 2 levels (LCN2; a proxy for inflammation), but we observed increased IL-17f and decreased IL-12α expression in the colon and decreased short chain fatty acid levels in the ADR-159 fed animals. Four weeks into the diet, half of the animals were dosed with Citrobacter to determine the effect of ADR-159 on infection and on pathogen induced colitis. Overall, our results suggest that while the ADR-159 diet does not prevent Citrobacter infection, it had an effect on Citrobacter-induced inflammation. In contrast to animals fed standard chow, ADR-159 fed animals did not show a reduction of small intestine length and increase of colon crypt depth, which occurred in control mice. These microbiological, histological, and immunological results provide evidence to support the impact of heat-treated microorganisms and their metabolites on the murine microbiome and health.

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Effect of genetic background and postinfectious stress on visceral sensitivity in Citrobacter rodentium‐infected mice

Cited by 17 publications

References 65 publications

Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome

Oral Administration of Heat-Treated Lactobacilli Modifies the Murine Microbiome and Reduces Citrobacter Induced Colitis

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