Acute effects of butyrate on intestinal permeability in patients with irritable bowel syndrome assessed by a novel colonoscopy research model

Abstract

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder for which effective treatment strategies are insufficient. Butyrate, a microbiota-derived short-chain fatty acid believed to strengthen the intestinal barrier function, might be a potential new treatment option. This study aimed to investigate potential protective effects of acute in vivo butyrate exposure on intestinal barrier function in healthy subjects and patients with IBS. For this, we used an experimental colonoscopy-perfusion model for colon-specific butyrate delivery and adequate tissue sampling. Seventeen IBS and 17 healthy subjects underwent a colonoscopy procedure exposing a predefined colonic area to 100 mmol/L butyrate for 90 min in vivo. Mucosal biopsies collected pre- and post-butyrate exposure were stimulated in Ussing chambers with/without sodium deoxycholate (DC) to induce intestinal hyperpermeability. Intestinal permeability was measured by fluorescein isothiocyanate-dextran and horseradish peroxidase passage. DC-stimulation significantly increased para- and transcellular permeability in biopsies collected pre-butyrate exposure. DC-induced transcellular hyperpermeability was significantly alleviated in biopsies collected post-butyrate exposure compared to pre-exposure in patients with IBS (p = 0.034). In conclusion, we established a colonoscopy research model for colon-specific delivery and sampling and demonstrated acute protective effects of butyrate on transcellular intestinal permeability in patients with IBS. The results support butyrate's potential role in novel treatment strategies in IBS. Clinicaltrials.gov number: NCT05249023.

Keywords: IBS; Ussing chamber; in vivo; intestinal barrier function.

Graphical abstract

Figure 1.

Experimental model used to collect colonic biopsies pre- and post-administration of butyrate in the human descending colon. This model uses double-balloon endoscopic equipment. Inflatable latex balloons are positioned at the tip of the working tube and the tip of the endoscope. Both balloons can be gently inflated to confine a well-defined area within the descending colon into which butyrate is administered. The figure shows the targeted area where butyrate is released (A), intestinal sampling before butyrate release (B), inflation of the distal balloon and butyrate release (C), inflation of the proximal balloon to ensure that the butyrate solution resides within the targeted area (D) and intestinal sampling post-exposure (E).

Figure 2.

Para- and transcellular permeability marker passage in colonic biopsies obtained from healthy subjects (blue circles) and patients with IBS (red, orange and yellow squares) pre- and post-butyrate exposure in vivo. Before exposure (pre-exposure) and 90 minutes after the in vivo exposure (post-exposure) to 100 mmol/L butyrate, colonic biopsies were left unstimulated (control) or stimulated with 1 mmol/L sodium deoxycholate (DC). Concentrations are shown with indicated median and interquartile range. *p < .05, **p < .01. n_Healthy = 17, n_IBS = 17.

Figure 3.

Effects of sodium deoxycholate on human colonic biopsies of healthy subjects (blue circles) and patients with IBS (red, orange and yellow squares) before and after in vivo butyrate exposure. Delta values of FITC-dextran and HRP passage (DC stimulated biopsy – control biopsy) are depicted to elucidate butyrate’s effect on DC-induced hyperpermeability. Delta values are shown with indicated median and interquartile range. *p < .05. n_Healthy = 17, n_IBS = 17.