Related Experiment Video
Updated: Jun 6, 2025
Investigating the Alleviating Effects of Bacillus cereus Administration on Colitis through Gut Microbiota Modulation
Published on: July 27, 2022
Effects of a Protease Inhibitor Camostat Mesilate on Gut Microbial Function in Patients with Irritable Bowel
Motoyori Kanazawa1, Kentaro Miyamoto2, Michiko Kano1
1Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Introduction:
Increased fecal protease activity, which may induce visceral hypersensitivity, has been observed in patients with irritable bowel syndrome (IBS). Serine proteases modulate FK506 binding protein (FKBP)-type peptidylprolyl cis-trans isomerase (PPIase) activity associated with immune and glucocorticoid receptor functions. The aim was to investigate whether camostat mesilate (CM), a serine protease inhibitor, modifies fecal bacterial function related to FKBP-type PPIases in patients with IBS.
Methods:
Randomly assigned 16 patients with IBS received 200 mg po tid of CM and 16 patients received placebo for 14 days. Self-reported adequate relief (AR) as a primary endpoint, IBS Symptom Severity Scale (IBS-SSS), and colonic motor and pain thresholds to colorectal distention were assessed before and after treatment. The fecal bacterial content was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and the Kyoto Encyclopedia of Genes and Genomes database.
Results:
CM significantly increased the relative abundance of Streptococcus and the functional abundances of serine protease and FKBP-type PPIase FkpA, FklB and SlyD more than placebo after treatment. CM treatment was not superior to placebo in proportion of AR although colonic motor response partially changed.
Conclusion:
CM modulated the fecal microbiome composition and functional potentials that are related to FKBP-type PPIase activity in IBS patients. These findings suggest that protease inhibitors may modify gut microbial function along with abnormal immunological and/or stress responses that underlie pathophysiology of IBS.
Insights
Camostat mesilate (CM), a protease inhibitor, altered gut bacteria function in irritable bowel syndrome (IBS) patients by increasing serine protease and FKBP-type PPIase activity. This suggests potential for targeting gut microbial function in IBS treatment.
Area of Science:
- Gastroenterology
- Microbiome research
- Pharmacology
Background:
- Irritable bowel syndrome (IBS) is linked to increased fecal protease activity, potentially causing visceral hypersensitivity.
- Serine proteases influence FKBP-type peptidylprolyl cis-trans isomerase (PPIase) activity, impacting immune and glucocorticoid receptor functions.
- Investigating serine protease inhibitors like camostat mesilate (CM) may reveal therapeutic targets for IBS.
Purpose of the Study:
- To determine if camostat mesilate (CM) modifies fecal bacterial function related to FKBP-type PPIases in IBS patients.
- To assess the impact of CM on IBS symptoms, colonic motor function, and pain thresholds.
- To explore changes in fecal microbiome composition and function following CM treatment.
Main Methods:
- A randomized, placebo-controlled trial involving 32 IBS patients treated with CM or placebo for 14 days.
- Assessment of adequate relief (AR), IBS Symptom Severity Scale (IBS-SSS), colonic motor, and pain thresholds pre- and post-treatment.
- Fecal 16S rRNA gene sequencing analyzed using PICRUSt and KEGG for microbiome composition and functional inference.
Main Results:
- CM significantly increased the abundance of Streptococcus and functional potential for serine protease and FKBP-type PPIases (FkpA, FklB, SlyD) compared to placebo.
- CM did not demonstrate superiority over placebo for adequate relief (AR).
- Colonic motor response showed partial changes following CM treatment.
Conclusions:
- Camostat mesilate modulated fecal microbiome composition and functional potentials related to FKBP-type PPIase activity in IBS patients.
- Protease inhibitors may represent a therapeutic strategy by modifying gut microbial function.
- These findings suggest a potential role for targeting protease activity in the pathophysiology of IBS, possibly influencing immunological or stress responses.
Related Concept Videos
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:21Drugs for Treatment of Constipation-Predominant IBS
01:17Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:30Irritable Bowel Syndrome III: Medical and Nursing Management