Repeated psychological stress is linked with irritable bowel syndrome-like symptoms

Irritable bowel syndrome (IBS) often comes with gastrointestinal symptoms in small and large intestines. IBS has been categorized into four subtypes depending on stool inconsistency; these are IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed (IBS-M), and unclassified IBS. But there is a lack of understanding in the scientific literature regarding the mechanisms and treatments of IBS. One of the reasons for this shortage of knowledge regarding IBS is the lack of useful experimental animal models.

Over the years, studies have suggested a link between emotional states and gut dysfunction, emphasizing on the existence and importance of the so-called ‘gut-brain axis’ in determining our emotional and metabolic wellbeing. Recently, chronic social defeat stress (cSDS) and chronic vicarious social defeat stress (cVSDS) have received acceptance as a model for major depressive disorder (MDD) and post-traumatic stress disorder. Could cVSDS animal models help us understand IBS in detail? To find out, researchers from Tokyo University of Science (TUS) led by Professor Akiyoshi Saitoh from the Faculty of Pharmaceutical Sciences, TUS, used cVSDS mice models. Their objective was to understand the effects of prolonged psychological stress on intestinal conditions. The team found that the psychological stress-induced mice showed higher intestinal transit ratio and visceral pain-related behaviors—hallmarks of IBS. Their findings were published on 6 October 2022 in the journal Frontiers in Neuroscience.

Elaborating on their study, Prof. Saitoh says, "We focused on the cVSDS paradigm and evaluated the impact of emotional stress on intestinal conditions. We further assessed the paradigm's potential as a novel animal model of IBS." In their study, they subjected mice to physical stress or emotional stress, in which the test animals either went through physical aggression or witnessed the aggression for 10 minutes per day for 10 consecutive days. On day 11, social interaction test was conducted to evaluate stress conditions of the test animals. Stress was also estimated through plasma corticosterone quantification, charcoal meal test, and capsaicin-induced hyperalgesia test of the animals. The researchers also evaluated the mice for intestinal permeability, pathology, defecation frequency, and stool content.

They found that the charcoal transit ratio, indicative of passage through the intestine, was significantly elevated in mice that underwent emotional stress compared to mice in the control (naïve) group not exposed to stress. However, the effects were insignificant in mice that underwent physical stress. The defecation frequency and stool water content were also increased in mice subjected to emotional stress. These effects lasted for 1 month after the stress loading. Additionally, there were no significant differences in the pathological status and intestinal permeability between the naïve and emotionally-stressed mice, suggesting no tissue-level changes due to stress. Professor Saitoh observes, "These results suggest that chronic stress in mice provokes IBS-D-like symptoms, such as chronic intestinal peristaltic exacerbations and abdominal hyperalgesia, without intestinal lesions."  Interestingly, the researchers found that the changes in intestinal motility in the test animals were ameliorated when the cVSDS mice were treated with keishikashakuyakuto, a kampo medicine clinically used for the treatment of IBS.

The study highlights the advantage of the cVSDS paradigm over traditional methods in inducing IBS-D-like symptoms through exposure to repeated psychological stress. Speaking about the mechanisms of these effects, Professor Saitoh surmises, "From the aspect of the gut–brain axis, we suspect that the insular cortex plays an important role in determining the phenotype of emotionally-stressed mice.” The insular cortex is a part of the upper central nervous system controlling digestive functions and is involved in the process of coping with psychological stress. 

In conclusion, this study demonstrates for the first time that cVSDS-induced psychological stress alone can cause IBS-D-like symptoms in mice. Further research could perhaps rely on cSDS and cVSDS paradigms for elucidating pathophysiological conditions and designing treatments for IBS.

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Reference                     

DOI: https://doi.org/10.3389/fnins.2022.993132

About The Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Akiyoshi Saitoh from Tokyo University of Science
Professor Saitoh is a Professor at the Faculty of Pharmaceutical Sciences at Tokyo University of Science, Tokyo, Japan. Where he specializes in neuropsychopharmacology and studies the pharmacological interventions for behavioral and neural disorders. Professor Saitoh extensively publishes in reputed journals and conferences in areas of Neurology, Neuroscience, and Pharmacology. He holds 4 patents and numerous refereed research papers in the field. 

Funding information
Funding received from the Cyclic Innovation for Clinical Empowerment as part of the Japan Agency for Medical Research and Development (AMED) under Grant Number 17pc0101018h0001