Source: Tokyo University of Science Irritable bowel syndrome (IBS) is often accompanied by gastrointestinal symptoms in the small and large intestine. 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 about the mechanisms and treatments of IBS. One of the reasons for this lack of knowledge about IBS is the lack of useful experimental animal models. Over the years, studies have suggested a link between emotional states and gut dysfunction, highlighting the existence and importance of the so-called “gut-brain axis” in determining our emotional and metabolic well-being. Recently, chronic social defeat stress (cSDS) and chronic vicarious social defeat stress (cVSDS) have been accepted as a model for major depressive disorder (MDD) and PTSD. 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 School of Pharmaceutical Sciences, TUS, used cVSDS mouse models. Their goal was to understand the effects of prolonged psychological stress on intestinal disease. The team found that mice induced with psychological stress exhibited a higher intestinal transit ratio and behaviors associated with visceral pain – hallmarks of IBS. Their findings were published in Frontiers in Neuroscience. Elaborating on their study, Professor Saitoh says, “we focused on the cVSDS paradigm and assessed the effect of emotional stress on intestinal disease. We further evaluated 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 animals either experienced physical aggression or witnessed the aggression for 10 minutes a day for 10 consecutive days. On the 11th day, a social interaction test was conducted to assess the stress conditions of the experimental animals. Anxiety was also assessed through plasma corticosterone quantification, the charcoal meal test, and the capsaicin-induced hyperalgesia test in animals. The researchers also assessed the mice for intestinal permeability, pathology, defecation frequency and stool content. They found that the ratio of carbon transit, indicative of intestinal transit, was significantly increased in mice subjected to emotional stress compared to mice in the control (naïve) group that were not exposed to stress. However, the effects were insignificant in mice subjected to physical stress. Defecation frequency and faecal water content were also increased in mice subjected to emotional stress. These effects lasted for 1 month after stress loading. Furthermore, there were no significant differences in pathological condition and intestinal permeability between naïve and emotionally stressed mice, suggesting no tissue-level changes due to stress. Over the years, studies have suggested a link between emotional states and gut dysfunction, highlighting the existence and importance of the so-called “gut-brain axis” in determining our emotional and metabolic well-being. The image is public Professor Saitoh says, “These results suggest that chronic stress in mice induces 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 lab animals were improved when the cVSDS mice were treated with keishikashakuyakuto, a kampo medicine used clinically to treat IBS. The study highlights the advantage of the cVSDS paradigm over traditional methods for inducing IBS-D-like symptoms through exposure to repeated psychological stress. Speaking about the mechanisms of these effects, Professor Saitoh says: “From the perspective of the gut-brain axis, we suspect that the insular cortex plays an important role in determining the phenotype of mice with emotional stress.” The insular cortex is part of the higher central nervous system that controls digestive functions and is involved in the process of dealing with psychological stress. In conclusion, this study demonstrates for the first time that cVSDS-induced psychological stress alone can induce IBS-D-like symptoms in mice. Further research could perhaps build on cSDS and cVSDS paradigms to elucidate pathophysiological conditions and design treatments for IBS.
About this stress research news
Author: Press Office Source: Tokyo University of Science Contact: Press Office – Tokyo University of Science Image: Image is in the public domain Original Research: Open Access. “Repeated psychological stress, chronic vicarious social defeat stress, induces irritable bowel syndrome-like symptoms in mice” by Toshinori Yoshioka et al. Frontiers in Neuroscience See also Abstract Repeated psychological stress, chronic social defeat stress, induces irritable bowel syndrome-like symptoms in mice A growing body of evidence has shown that emotional states and gut diseases are interconnected in so-called “brain-gut interactions.” Indeed, many psychiatric disorders are accompanied by gastrointestinal symptoms, such as irritable bowel syndrome (IBS). However, the functional link remains unknown, in part because there are few useful animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders such as depression, known as chronic vicarious social stress (cVSDS) mice, which we primed using exposure to repeated psychological stress and then examined their gut states. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over a month after the stress session. On the other hand, pathological evaluations of histological and inflammatory scores of naïve mice and the cVSDS model did not differ. In addition, keishikashakuyakuto—a kampo medicine used clinically to treat IBS—normalized the change in intestinal motility in cVSDS model mice. Our results indicate that cVSDS model mice exhibit IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organ damage. Therefore, we propose the cVSDS paradigm as a new animal model of IBS with broad validity, elucidating the association between depressive states and intestinal abnormalities.
