Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats

Takajo, Takeshi; Tomita, Kengo; Tsuchihashi, Hanae; Enomoto, Shingo; Tanichi, Masaaki; Toda, Hiroyuki; Okada, Yoshikiyo; Furuhashi, Hirotaka; Sugihara, Nao; Wada, Akinori; Horiuchi, Kazuki; Inaba, Kenichi; Hanawa, Yoshinori; Shibuya, Naoki; Shirakabe, Kazuhiko; Higashiyama, Masaaki; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Kimura, Katsunori; Miura, Soichiro; Shimizu, Kunio; Hokari, Ryota

doi:10.5009/gnl18296

Cited by 31 publications

(19 citation statements)

References 30 publications

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“…The use of questionnaires does not focus on this relationship and the long-term observation time needed precludes conclusions as regards to the onset of disease or symptoms. Animal models may be useful to reveal possible etiological factors related to the onset of gastrointestinal symptoms [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults

et al. 2020

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Background >Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. Methods Gastrointestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale- Self assessment (MADRS-S). Trait anxiety was estimated with three of the Swedish universities of Personality (SSP) scales: Somatic trait anxiety, Psychic trait anxiety and Stress susceptibility. Self-ratings were collected from 491 young adult psychiatric outpatients and 85 healthy controls. Gastrointestinal symptom severity was compared between patients with and without current psychotropic medication and controls. Associations between gastrointestinal symptoms, depressive symptoms and trait anxiety were assessed using Spearman’s coefficients and generalized linear models adjusting for possible confounders (sex, body mass index, bulimia nervosa). Results Patients, with and without current psychotropic medication, reported significantly more gastrointestinal symptoms than controls. In the generalized linear models, total MADRS-S score (p < 0.001), Somatic trait anxiety (p < 0.001), Psychic trait anxiety (p = 0.002) and Stress susceptibility (p = 0.002) were independent predictors of the total GSRS-IBS score. Further exploratory analysis using unsupervised learning revealed a diverse spectrum of symptoms that clustered into six groups. Conclusion Gastrointestinal symptoms are both highly prevalent and diverse in young adult psychiatric outpatients, regardless of current psychotropic medication. Depressive symptom severity and degree of trait anxiety are independently related to the total gastrointestinal symptom burden.

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Section: Discussionmentioning

confidence: 99%

A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults

et al. 2020

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“…Lee et al (2017) similarly found that severe depressive symptoms were associated with a high odds ratio for IBS [ 40 ]. Empirical evidence also indicates that psychosomatic symptoms, such as depression, result in a two-fold increase in the onset of gastrointestinal symptoms in IBS [ 44 , 45 ].…”

Section: Irritable Bowel Syndrome and Depressionmentioning

confidence: 99%

Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

et al. 2021

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Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut−brain axis—a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

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“…We performed high‐throughput sequencing of gut microbiota by using the cecal contents in the same way as described in our previous study 19 …”

Section: Methodsmentioning

confidence: 99%

“…Leukocytes were isolated from the spleen. Leukocytes were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE, Thermo Fisher Scientific, Waltham, MA, USA) at the concentration of 15.6 μM 19 . In some experiments, leukocytes were incubated with the antibody for β 7 integrin (FIB27, BD PharMingen) at a concentration of 100 μg/mL before fluorescent staining.…”

Section: Methodsmentioning

confidence: 99%

Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa

Hanawa

Higashiyama

Kurihara

et al. 2021

J of Gastro and Hepatol

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Background and Aim The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease‐like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. Methods Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF‐α, IFN‐γ, IL1‐β, MAdCAM‐1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Immunohistochemistry was performed to examine the expression of MAdCAM‐1 in the small intestine. The composition of gut microbiota was assessed using high‐throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. Results Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP‐1R and GLP‐2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. Conclusion Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non‐caloric artificial sweeteners may not be as safe as we think.

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Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats

Cited by 31 publications

References 30 publications

A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults

A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults

Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa

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