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. 2023 Sep 20;12(18):6064.
doi: 10.3390/jcm12186064.

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial

Aleksandra Kovaleva  1 , Elena Poluektova  1   2 , Roman Maslennikov  1   2 , Anna Karchevskaya  1   3   4 , Oleg Shifrin  1 , Andrey Kiryukhin  5 , Aleksandr Tertychnyy  6 , Leonid Kovalev  7 , Marina Kovaleva  7 , Olga Lobanova  6 , Anna Kudryavtseva  8 , George Krasnov  8 , Maria Fedorova  8 , Vladimir Ivashkin  1   2
Affiliations

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial

Aleksandra Kovaleva et al. J Clin Med. .

Abstract

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.

Keywords: dysbiosis; functional bowel disease; gut microbiota; intestinal permeability; minimal inflammation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biopsy of the duodenal mucosa of a patient with diarrhea-predominant irritable bowel syndrome and functional dyspepsia overlap. Magnification ×400. Hematoxylin-eosin staining. The patient sample shows lymphocytic infiltration (↓) (11 to 15 lymphocytes per 100 epithelial cells, corresponding to Group 3) and an increased number of eosinophils (*) (mean number is 6.8 in the standard field of view).
Figure 2
Figure 2
Immunohistochemical staining of the duodenal mucosa for MUC-2 glycoprotein in a patient with diarrhea-predominant irritable bowel syndrome and functional dyspepsia overlap. Magnification ×400. In the patient sample, staining of 5–10% of the cells is noted, which corresponds to group 2.
Figure 3
Figure 3
CONSORT 2010 Flow Diagram.
Figure 4
Figure 4
The changes in the total score of 7 × 7 (a) and GSRS (b) scales as a result of using trimebutine (TRI group), rebamipide (REB group), and both drugs simultaneously (T + R group) in patients with diarrhea-predominant irritable bowel syndrome and functional dyspepsia overlap.
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