Short chain fatty acids and colon motility in a mouse model of irritable bowel syndrome

Ilnar F Shaidullov,Anton Hermann,Sayar R Abdulkhakov,Dina M Sorokina,Farit G Sitdikov,Guzel F Sitdikova

doi:10.1186/s12876-021-01613-y

Ilnar F Shaidullov, Anton Hermann + Show 4 more

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https://doi.org/10.1186/s12876-021-01613-y

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Journal: BMC gastroenterology	Publication Date: Jan 26, 2021
Citations: 38	License type: open-access

Affiliation: University of Salzburg

Abstract

BackgroundIrritable bowel syndrome (IBS) is defined as a multifactorial disorder associated with visceral hypersensitivity, altered gut motility and dysfunction of the brain-gut axis. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. Short chain fatty acids (SCFAs) induce both inhibitory and stimulatory action on colon motility, however, their effects on the IBS model were not investigated. The aim of our study was to investigate the level of SFCAs in feces and their effects on colon motility in a mouse model of IBS.MethodsIBS model was induced in mice by intracolonic infusion of 1% acetic acid during the early postnatal period. Mice colon hypersensitivity was assessed by the threshold of the abdominal withdrawal reflex in response to colorectal distention. Colon contractility was studied using proximal colon specimens in isometric conditions. Transit rates were assessed by the pellet propulsion in the isolated colon. Concentrations of SCFAs in feces were measured using gas–liquid chromatography.ResultsThe concentration of SCFAs in feces of IBS model mice was higher compared to the control group. Visceral sensitivity to colorectal distension and colonic transit rate were increased indicating IBS with predominant diarrhea. The frequency and amplitude of spontaneous contractions of proximal colon segments from IBS mice were higher, but carbachol induced contractions were lower compared to control. During acute application of SCFAs (sodium propionate, sodium acetate or butyric acid) dose-dependently (0.5–30 mM) decreased tonic tension, frequency and amplitude of spontaneous and carbachol-evoked contractions. In the mouse IBS group the inhibitory effects SCFAs on spontaneous and carbachol-evoked contractions were less pronounced. At the same time intraluminal administration of butyrate (5 mM) increased the transit rate in the colon of both groups, but its stimulatory effect was more pronounced in mouse IBS model group.ConclusionOur data indicate that the increased transit rate in the mouse IBS model group is associated with a disbalance of activating and inhibiting action of SCFAs due to chronically elevated SCFA levels, which may impact the pathogenesis of IBS with predominant diarrhea syndrome.

Highlights

Irritable bowel syndrome (IBS) is defined as a multifactorial disorder associated with visceral hypersensitivity, altered gut motility and dysfunction of the brain-gut axis
Contractility of mouse colon segments and transit rate To study the effect of Short chain fatty acids (SCFAs) on gastrointestinal contractility, we analyzed parameters of contractile activity of proximal colon segments which demonstrated spontaneous activity starting about 45 min after mounting the specimen (Fig. 1a)
In conclusion, our results indicate that in mouse IBS model the chronically elevated SCFA level is associated with an accelerated colonic transit and an increased amplitude and frequency of contractions of the proximal colon specimen

Summary

Introduction

Irritable bowel syndrome (IBS) is defined as a multifactorial disorder associated with visceral hypersensitivity, altered gut motility and dysfunction of the brain-gut axis. Short chain fatty acids (SCFAs) induce both inhibitory and stimulatory action on colon motility, their effects on the IBS model were not investigated. The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder defined by a variable combination of chronic or recurrent gastrointestinal symptoms including abdominal pain and changed bowel habits as a result of altered intestinal motility, dysfunction of the brain-gut. Inhibitory effects of SCFAs at physiological concentrations (10–30 mM) [15] were proposed to be mediated by the enteric nervous system [16] and release of the antimotility peptide YY (PYY) from enteroendocrine cells [17, 18]. At the same time in mucosa attached preparations SCFAs stimulated contractility in low concentrations (1–10 mM) [19,20,21,22] suggesting a role of paracrine or hormonal agents like serotonin released from enteroendocrine cells [13]

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