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Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Psychological stress is a putative incentive to intestinal mucosal inflammation. Schneider et al. unraveled a dynamic network during intestinal inflammation under psychological stress. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: In patients with colitis, the high comorbidity of depressive disorders is well-known, but the detailed mechanisms remain unresolved. In this study, we examined whether colitis induced by dextran sulfate sodium (DSS) increased the susceptibility to chronic unpredictable mild stress (CUMS) in C57BL/6J mice with resilience to CUMS., Main Methods: To induce experimental colitis and depressive-like behaviors, male 7-weeks old C57BL/6J mice were administered ad libitum 1% DSS solution for 11 days, and subjected to various mild stressors in a chronic, inevitable and unpredictable way according to a random schedule for 21 days, respectively., Key Findings: In naïve mice exposed to CUMS, their immobility times in a forced swim (FS) test were almost equal to those in control mice. The DSS administration to naïve mice induced colitis without depressive-like behavior, and at 18 days after termination of the DSS administration, the colitis had recovered to control levels, while altered diversity and composition of bacterial genera such as Bacteroides spp., Alistipes spp., etc., were found in the gut microbiota. Exposure of mice with DSS-induced colitis to CUMS (DSS + CUMS) significantly increased the immobility times in the FS test. In the gut microbiota of DSS + CUMS mice, the alteration profile of the relative abundance of bacterial genera differed from in the DSS ones., Significance: These findings indicate that mice with colitis exhibit increased susceptibility to psychological stress, resulting in induction of depressive-like behavior, and this might be due, at least in part, to altered characteristics of the gut microbiota., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Inflammatory bowel diseases (IBD) are a group of chronic gastrointestinal tract disorders with complex etiology, with intestinal dysbiosis as the most prominent factor. In this study, we assessed the anti-inflammatory and antibacterial actions of the human cathelicidin LL-37 and its shortest active fragment, KR-12 in the mouse models of colitis., Materials and Methods: Mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and dextran sulfate sodium (DSS) were used in the study. The extent of inflammation was evaluated based on the macro- and microscopic scores, quantification of myeloperoxidase (MPO) activity and microbiological analysis of stool samples., Results: A preliminary study with LL-37 and KR-12 (1 mg/kg, ip, twice daily) showed a decrease in macroscopic and ulcer scores in the acute TNBS-induced model of colitis. We observed that KR-12 (5 mg/kg, ip, twice daily) reduced microscopic and ulcer scores in the semi-chronic and chronic TNBS-induced models of colitis compared with inflamed mice. Furthermore, qualitative and quantitative changes in colonic microbiota were observed: KR-12 (5 mg/kg, ip, twice daily) decreased the overall number of bacteria, Escherichia coli and coli group bacteria. In the semi-chronic DSS-induced model, KR-12 attenuated intestinal inflammation as demonstrated by a reduction in macroscopic score and colon damage score and MPO activity., Conclusions: We demonstrated that KR-12 alleviates inflammation in four different mouse models of colitis what suggests KR-12 and cathelicidins as a whole are worth being considered as a potential therapeutic option in the treatment of IBD.

Excessive expression of interleukin (IL)-1β in the brain causes depression and cognitive dysfunction. Herein, we investigated the effect of Lactobacillus gasseri NK109, which suppressed IL-1β expression in activated macrophages, on Escherichia coli K1-induced cognitive impairment and depression in mice. Germ-free and specific pathogen-free mice with neuropsychiatric disorders were prepared by oral gavage of K1. NK109 alleviated K1-induced cognition-impaired and depressive behaviors, decreased the expression of IL-1β and populations of NF-κB + /Iba1 + and IL-1R + cells, and increased the K1-suppressed population of BDNF + /NeuN + cells in the hippocampus. However, its effects were partially attenuated by celiac vagotomy. NK109 treatment mitigated K1-induced colitis and gut dysbiosis. Tyndallized NK109, even if lysed, alleviated cognitive impairment and depression. In conclusion, NK109 alleviated neuropsychiatric disorders and colitis by modulating IL-1β expression, gut microbiota, and vagus nerve-mediated gut-brain signaling.

Jung understood dissociation as a natural state of the psyche, capable of turning defensive through development. Based on this premise, and its conception on the equivalence between psyche and matter, the present work describes the un-doing of a dissociation expressed through a chronic enterocolitis disorder. When the symbol remains closer to the body and its most instinctive manifestations, we need to descend to that level in order to let the vertical axis connection be gradually restored through the therapeutic relationship - the horizontal axis. In other words, this un-doing requires that patient and analyst follow the unconscious path proposed by symbolic expressions that gradually emerge through the patient's body and active imagination. Movement is our most primitive and fundamental experience. Many authors (Stern, Panksepp, Gallese) have agreed that, in addition to being first in terms of development, movement continues to have primacy over any other experience throughout life. This means that emotions, bodily concepts and, later, speech, evolve from a somatic basis. In the light of such neuroscientific findings, Jung's vision of the correspondence of psyche and matter will be revisited in order to portray how the analytic bond provides a context for the re-establishment of the linking/creative function of the archetype, and allows the restoring of the ego-Self axis connection by including non-verbal approaches, such as body-based active imagination, also known as Authentic Movement. Authentic Movement is an amplification of Jung's active imagination method that enables a dialogue between the ego and the diverse configurations of the unconscious. When such dialogue is grounded in the body, there is an easier access to the affective dimension stored in implicit memory. That which was relived through the body can gradually be remembered, and affects hitherto rejected, find other symbolic ways of being expressed and contained in the analytic vas., (© 2020, The Society of Analytical Psychology.)

Gut microbes play significant roles in colitis development. The current study was aimed to uncover the preventive effects of lycopene (LYC), a functional carotenoid component, on colitis and the accompanied behavior disorders. The current study demonstrated that LYC treatment (50 mg/kg body weight/day) for 40 days prevented the dextran sulfate sodium (DSS)-induced gut barrier damages and inflammatory responses in male mice. LYC improved DSS-induced depression and anxiety-like behavioral disorders by suppressing neuroinflammation and prevented synaptic ultrastructure damages by upregulating the expressions of neurotrophic factor and postsynaptic-density protein. Moreover, LYC reshaped the gut microbiome in colitis mice by decreasing the relative abundance of proteobacteria and increasing the relative abundance of Bifidobacterium and Lactobacillus . LYC also elevated the generation of short-chain fatty acids and inhibited the permeability of lipopolysaccharide in colitis mice. In conclusion, LYC ameliorate DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance.

Inflammatory bowel disease (IBD) is characterized by relapsing periods of gut inflammation, and is comorbid with depression, anxiety, and cognitive deficits. Animal models of IBD that explore the behavioral consequences almost exclusively use acute models of gut inflammation, which fails to recapitulate the cyclic, chronic nature of IBD. This study sought to identify behavioral differences in digging, memory, and stress-coping strategies in mice exposed to one (acute) or three (chronic) cycles of gut inflammation, using the dextran sodium sulfate (DSS) model of colitis. Similar levels of gut pathology were observed between acute and chronically exposed mice, although mice in the chronic treatment had significantly shorter colons, suggesting more severe disease. Behavioral measures revealed an unexpected pattern in which chronic treatment evoked fewer deficits than acute treatment. Specifically, acutely-treated mice showed alterations in measures of object burying, novel object recognition, object location memory, and stress-coping (forced swim task). Chronically-treated animals, however, showed similar alterations in object burying, but not the other measures. These data suggest an adaptive or tolerizing effect of repeated cycles of peripheral gut inflammation on mnemonic function and stress-coping, whereas some other behaviors continue to be affected by gut inflammation. We speculate that the normalization of some functions may involve the reversion to the baseline state of the hypothalamic-pituitary-adrenal axis and/or levels of neuroinflammation, which are both activated by the first exposure to the colitic agent., (Copyright © 2020. Published by Elsevier Inc.)

Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium . These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals' diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli , normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Depression and anxiety-related psychological symptoms are increasingly recognised as important co-morbidities in patients with inflammatory bowel disease (IBD). Dextran sulfate sodium (DSS) -induced colitis is an animal model of IBD in which afferent activation of the gut-brain axis can be assessed and explored as a source of behavioural change. Exposure of adult male Wistar rats to DSS (5%) in drinking water induced distal colitis. In parallel to local inflammatory responses in the gut wall, increased expression of IL-6 and iNOS was found in the cerebral cortex and an increase in ventricular volume. Immunoreactivity of immediate early gene FosB/ΔFosB activation was measured as an index of cellular activation and was increased in the nucleus accumbens and dorsal raphe nucleus in acutely colitic animals. Following resolution of the acute colitic response, sustained anhedonia in the saccharin preference test, immobility in the forced swim test, reduced burying behaviour in the marble burying test, and mild signs of anxiety in the elevated plus maze and light/dark box were observed. Central increases in iNOS expression persisted during the recovery phase and mapped to reactive microglia, particularly those found in the parenchyma surrounding circumventricular regions. Evidence of associated nitration was also found. Sustained increases in ventricular volume and reduced T2 magnetic resonance relaxometry time in cortical regions were observed during the recovery period. FosB/ΔFosB activation was evident in the dorsal raphe during recovery. Persistent central inflammation and cellular activation may underpin the emergence of symptoms of depression and anxiety in experimental colitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15-45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1 ) a visceral hypersensitivity ( P = 0.03), 2 ) an increased colon weight-to-length ratio ( P = 0.01), 3 ) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4 ) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae. NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

The gut dysbiosis by stressors such as immobilization deteriorates psychiatric disorders through microbiota-gut-brain axis activation. To understand whether probiotics could simultaneously alleviate anxiety/depression and colitis, we examined their effects on immobilization stress (IS)-induced anxiety/depression and colitis in mice. The probiotics Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 were isolated from healthy human feces. Mice with anxiety/depression and colitis were prepared by IS treatment. NK33 and NK98 potently suppressed NF-κB activation in lipopolysaccharide (LPS)-induced BV-2 cells. Treatment with NK33 and/or NK98, which were orally gavaged in mice before or after IS treatment, significantly suppressed the occurrence and development of anxiety/depression, infiltration of Iba1⁺ and LPS⁺/CD11b⁺ cells (activated microglia) into the hippocampus, and corticosterone, IL-6, and LPS levels in the blood. Furthermore, they induced hippocampal BDNF expression while NF-κB activation was suppressed. NK33 and/or NK98 treatments suppressed IS-induced colon shortening, myeloperoxidase activity, infiltration of CD11b⁺/CD11c⁺ cells, and IL-6 expression in the colon. Their treatments also suppressed the IS-induced fecal Proteobacteria population and excessive LPS production. They also induced BDNF expression in LPS-induced SH-SY5Y cells in vitro. In conclusion, NK33 and NK98 synergistically alleviated the occurrence and development of anxiety/depression and colitis through the regulation of gut immune responses and microbiota composition.

Background & Aims: Psychological stress, in early life or adulthood, is a significant risk factor for inflammatory disorders, including inflammatory bowel diseases. However, little is known about the mechanisms by which emotional factors affect the immune system. γ-Aminobutyric acid type A receptors (GABA A Rs) regulate stress and inflammation, but it is not clear whether specific subtypes of GABA A Rs mediate stress-induced gastrointestinal inflammation. We investigated the roles of different GABA A R subtypes in mouse colon inflammation induced by 2 different forms of psychological stress., Methods: C57BL/6J mice were exposed to early-life stress, and adult mice were exposed to acute-restraint stress; control mice were not exposed to either form of stress. We collected colon tissues and measured contractility using isometric tension recordings; colon inflammation, based on levels of cluster of differentiation 163 and tumor necrosis factor messenger RNA (mRNA) and protein and myeloperoxidase activity; and permeability, based on levels of tight junction protein 1 and occludin mRNA and protein. Mice were given fluorescently labeled dextran orally and systemic absorption was measured. We also performed studies of mice with disruption of the GABA A R subunit α3 gene (Gabra3 -/- mice)., Results: Mice exposed to early-life stress had significantly altered GABA A R-mediated colonic contractility and impaired barrier function, and their colon tissue had increased levels of Gabra3 mRNA compared with control mice. Restraint stress led to colon inflammation in C57/BL6J mice but not Gabra3 -/- mice. Colonic inflammation was induced in vitro by an α3-GABA A R agonist, showing a proinflammatory role for this receptor subtype. In contrast, α1/4/5-GABA A R ligands decreased the expression of colonic inflammatory markers., Conclusions: We found stress to increase expression of Gabra3 and induce inflammation in mouse colon, together with impaired barrier function. The in vitro pharmacologic activation of α3-GABA A Rs recapitulated colonic inflammation, whereas α1/4/5-GABA A R ligands were anti-inflammatory. These proteins might serve as therapeutic targets for treatment of colon inflammation or inflammatory bowel diseases., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely exacerbated colitis, which was evaluated by both colorectal tissue weight and histological score of colitis. rWAS treatment increased mRNA expression of UCN2 and IFN-γ in large intestinal lamina propria mononuclear cells (LI-LPMC). Interestingly, exacerbated colitis was associated with changes in the microbial community of MACB, specifically loss of bacterial species diversity and an increase in the component ratio of Clostridium, revealed by 16S rRNA gene amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus strain was protective against the exacerbation of colitis and was associated with a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken together, these results suggested that loss of species diversity in MACB might play a key role in exacerbated colitis induced by chronic psychological stress. In addition, probiotic treatment may be used as a tool to preserve the diversity of bacterial species in MACB and alleviate gut inflammation induced by psychological stress.

Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-α) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30-60 min before behavioral test. Colitis was confirmed by increased colonic TNF-α level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-α, iNOS expression and nitrite content. Acute NOS inhibition using either Nω-nitro-l-arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-α level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders., (Copyright © 2015. Published by Elsevier Inc.)

Aim: To investigate the effects of restraint stress on chronic colitis in interleukin (IL)-10 deficient (IL-10(-/-)) mice., Methods: The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10(-/-) mice. Both wild-type and IL-10(-/-) mice were physically restrained in a well-ventilated, 50 cm(3) conical polypropylene tube for 2 h per day for three consecutive days. The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10(-/-) mice. The IL-10(-/-) mice were exposed to restraint stress for 2 h per day for 3 consecutive days, and then treated with piroxicam for 4 d at a dose of 200 ppm administered in the rodent chow., Results: In the first experiment, none of the wild-type mice with or without restraint stress showed clinical and histopathological abnormality in the gut. However, IL-10(-/-) mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress. In the second experiment, restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10(-/-) mice. Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress., Conclusion: This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.

Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model., Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier., Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4., Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8-12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups (P < 0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions (P < 0.05). Contrary to our hypothesis, the α-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED (P < 0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region., (Copyright © 2015 the American Physiological Society.)

Objective: The dysfunction of immune regulation plays a critical role in the pathogenesis of a number of chronic inflammatory disorders, such as IBD. A close relationship between psychological stress and intestinal inflammation has been noted; the underlying mechanism remains elusive. This study aims to elucidate a pathological pathway between psychological stress and the dysfunction of regulatory T cells (Treg), and its effect on facilitating intestinal inflammation., Design: A restraint stress model was employed to induce psychological stress in mice. The functions of Tregs were determined by assessing the immune suppressor effects in the intestine. A mouse model of intestinal inflammation was established using a low dose of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) together with the challenge of chronic stress., Results: After treating mice with restraint stress, the suppressor function of intestinal Treg was compromised, although the frequency of Treg was not changed in the intestine. Further observation revealed that stress induced Tregs in the intestine to differentiate into foxhead box P3(+) interleukin (IL)-17(+) tumour necrosis factor (TNF)-α(+) T cells. We also observed that exposure to stress-derived prolactin induced dendritic cells (DC) to produce IL-6 and IL-23 in vitro and in vivo, which played a critical role in altering Treg's phenotypes. Treating mice with chronic stress facilitated the initiation of intestinal inflammation by a low dose of TNBS or DSS, which was abolished by pretreatment with an inhibitor of prolactin, the cabergoline., Conclusions: Psychological stress-derived prolactin alters DC and Treg's properties to contribute to intestinal inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

Aim: To investigated the incidence of diversion colitis (DC) and impact of DC symptoms on quality of life (QoL) after ileostomy reversal in rectal cancer., Methods: We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery, Korea University Anam Hospital. The participants totally underwent two rounds of the examinations. At first examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations. At second examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals. Clinicopathological data were based on the histopathological reports and clinical records of the patients., Results: At the first examination, all of the patients presented with inflammation, which was mild in 15 (50%) patients, moderate in 11 (36.7%) and severe in 4 (13.3%) by endoscopy and mild in 14 (46.7%) and moderate in 16 (53.3%) by histology. At the second examination, only 11 (36.7%) and 17 (56.7%) patients had mild inflammation by endoscopy and histology, respectively. There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination. The symptoms detected on the first and second questionnaires were mucous discharge in 12 (40%) and 5 (17%) patients, bloody discharge in 5 (17%) and 3 (10%) patients, abdominal pain in 4 (13%) and 2 (7%) patients and tenesmus in 9 (30%) and 5 (17%) patients, respectively. We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge, bleeding, abdominal pain and tenesmus in both time points. Diarrhea was detected in 9 patients at the second examination; this number correlated with the severity of DC (0%, 0%, 66.7%, 33.3% vs 0%, 71.4%, 23.8%, 4.8%, P = 0.001) and the symptom-related QoL (r = -0.791, P < 0.001)., Conclusion: The severity of DC is related to diarrhea after an ileostomy reversal and may adversely affect QoL.

Recurrent episodes of cutaneous and subcutaneous ulcers, especially in the oral cavity, represent a high psychological and painful burden for the patient. If there in addition are symptoms of arthralgia and/or colitis, an autoimmune disease with vasculitis, particularly a Morbus Behçet has to be considered as a possible differential diagnosis. The therapy therefore would be an immunosuppressive one. Also a wide immunologic diagnostic process has to be started. Furthermore, a chronic inflammatory bowel disease has to be excluded by colonoscopic biopsy. An infectious etiology of the symptoms (viral/bacterial/parasitic) should be investigated by microbiological and laboratory tests. A thrush or a herpes-infection caused by immunosuppression (toxic or due to illness) has to be considered as a further differential diagnosis. Also a precise medical and drug history is very important because of possible toxic adverse effects. Until confirmation of a final diagnosis, only a symptomatic analgetic or antifungal or antiviral therapy in case of a positive thrush or herpes culture respectively should be initiated with respect to the very different kinds of treatment of the diseases included in the differential diagnosis.

Background & Aims: Patients with inflammatory bowel disease (IBD) frequently also have depression, yet little is known of its role in IBD pathogenesis. We investigated whether the development of depression after the establishment of chronic inflammation reactivates an acute relapse of IBD and underlying pharmacologic mechanisms in mouse models., Methods: Colitis was induced by administration of dextran sulfate sodium (DSS) or dinitrobenzenesulfonic acid to C57BL/6 mice. Depression was induced by olfactory bulbectomy or chronic intracerebroventricular injection of reserpine. Colitis was reactivated by subsequent exposure to DSS or dinitrobenzenesulfonic acid. Some mice were given the antidepressant desmethylimipramine. Acute DSS-colitis was induced in mice lacking the alpha 7 subunit of the nicotinic acetylcholine receptor (alpha 7nAchR), and vagotomy was performed. Disease severity and colon tissue histology and inflammation were evaluated. Levels of C-reactive protein and proinflammatory cytokines were determined by enzyme-linked immunosorbent assay analysis of colon samples and macrophage culture., Results: Induction of depression reactivated inflammation in mice in which colitis had been established and become quiescent. The induction was associated with impaired cholinergic inhibition of proinflammatory cytokine secretion by macrophages and mediated by alpha 7nAchR on these cells; macrophages isolated from depressed mice showed increased proinflammatory cytokine secretion. Depression-induced reactivation of colitis was prevented by desmethylimipramine and accompanied by a normalization of proinflammatory cytokine secretion., Conclusions: Depression reactivates dormant chronic colitis via the alpha 7nAchR. These findings encourage closer monitoring of behavior for signs of depression in IBD patients because treatment might prevent inflammatory conditions. Furthermore, alpha 7nAchR agonists might achieve this effect without the need for psychotropic medication.

Early life stress enhances the vulnerability to both mood and chronic inflammatory disorders, suggesting a link between these stress-related disorders. To study this, we exposed male C57BL/6 mice to early life stress [maternal separation (MS), 3 h/d, d 1-14] and to adult chronic psychosocial stress [chronic subordinate colony housing (CSC)] and measured changes in neuroendocrine parameters and in the severity of a chemically induced colitis. In both unseparated and MS mice, 19 d of CSC exposure resulted in a transient decrease in body weight gain, increased anxiety-related behavior, and decreased vasopressin mRNA expression in the hypothalamic paraventricular nucleus compared with respective nonstressed mice. However, only CSC-stressed MS mice showed elevated CRH mRNA expression in the paraventricular nucleus and reduced plasma corticosterone. Subsequent treatment with dextran sulfate sodium (1%, 7 d) resulted in a more severe colonic inflammation in MS compared with unseparated mice. This was indicated by an increased histological damage score and increased TNF secretion (nonstressed MS mice), more severe body weight loss and inflammatory reduction in colon length (CSC-stressed MS mice), and increased interferon-gamma secretion (nonstressed and CSC-stressed MS mice). In conclusion, early life stress and subsequent exposure to chronic psychosocial stress in adulthood induced neuroendocrine abnormalities, which likely contributed to enhanced vulnerability to chemically induced colitis. The combined use of MS and CSC represents a potential animal model providing novel (patho)physiological insights into the complex interactions between neuroendocrine and inflammatory actions upon chronic stress exposure. These findings may further help to reveal mechanisms of hypocortisolemic disorders.

The IMPACT questionnaire was developed in Canada to measure quality of life in children with inflammatory bowel disease (IBD). In the present study, 20 children with IBD completed 2 versions of the IMPACT questionnaire with a Likert scale or visual analog scale (VAS), 5 of whom expressed problems with language or phrasing. Difficult words included "restrictions," "moderate," "diarrhea," "school break," and the abbreviation "IBD." Fifteen children preferred the Likert scale to the VAS (chi = 20, P < 0.01). Rewording the difficult words and using a Likert scale should facilitate completion of the IMPACT questionnaire in the United Kingdom. Further validation is needed to ensure that the instrument is reliable and valid.

Epidemiological studies have shown that exercise protects the gastrointestinal tract, reducing the risk of diverticulosis, gastrointestinal haemorrhage and inflammatory bowel disease, while many digestive complaints occurring during exercise are attributed to the adverse effects of exercise on the colon. In order to assess the effects of regular exercise on the pathogenesis of colitis, Sprague-Dawley rats of both sexes were either kept sedentary or given exercise on a running wheel (0.4 km h(-1), 30 min for 3 days week(-1)). At the end of 6 weeks, under anaesthesia, either saline or acetic acid (4%, 1 ml) was given intracolonically. Holeboard tests were performed for the evaluation of anxiety at 24 h before and 48 h after induction of colitis. Increased 'freezing time' in the colitis-induced sedentary group, representing increased anxiety, was reduced in the exercised colitis group (P < 0.05). On the third day following the colonic instillation, the rats were decapitated under brief ether anesthesia and the distal 8 cm of the colons were removed. In the sedentary colitis group, macroscopic and microscopic damage scores, malondialdehyde level and myeloperoxidase activity were increased when compared to the control group (P < 0.01-0.001), while exercise prior to colitis reduced all the measurements with respect to sedentary colitis group (P < 0.05-0.001). The results demonstrate that low-intensity, repetitive exercise protects against oxidative colonic injury, and that this appears to involve the anxiolytic effect of exercise, suggesting that exercise may have a therapeutic value in reducing stress-related exacerbation of colitis.

Background & Aims: Psychiatric factors may determine gastrointestinal health outcomes. Here, we used a model of depression based on neonatal maternal separation (MS) to identify alterations in gut physiology and to assess its association with increased sensitivity to experimental colitis in adulthood. We also examined whether antidepressant therapy attenuates the increased susceptibility to colitis., Methods: C57BL/6 mouse pups were separated from mothers for 3 hours per day at 1-21 days of age. Maternally unseparated (US) litters served as controls. At 8 weeks of age mice were examined for changes in behavior, intestinal permeability, and sensitivity to colitis. Separate sets of MS and US mice were given either saline or the antidepressant desipramine 15 mg/kg once daily at 23-36 days of age. Testing of mice occurred at 8 weeks of age., Results: Adult MS mice showed evidence of depressive-like behavior and enhanced intestinal permeability but showed no evidence of spontaneous inflammation. A more severe colitis was seen in MS compared with US mice. Antidepressant therapy improved parameters of depressive-like behavior and reduced the vulnerability to dextran sulphate sodium colitis in MS mice but had no effect on colitis in US mice., Conclusions: MS may lead to depression and increased responsiveness to stress, to impaired intestinal barrier function, and to enhanced vulnerability to colitis in adulthood. This vulnerability is reversed by antidepressant therapy. Depression increases vulnerability to intestinal inflammation. We speculate that pre-existing depression may facilitate the expression of inflammatory bowel diseases.

Hydrogen sulfide (H(2)S) functions as a neuromodulator, but whether it modulates visceral perception and pain is unknown. Cystathionine beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) mediate enzymatic generation of H(2)S in mammalian cells. Here we have investigated the role of H(2)S in modulating nociception to colorectal distension, a model that mimics some features of the irritable bowel syndrome. Four graded (0.4-1.6 ml of water) colorectal distensions (CRDs) were produced in conscious rats (healthy and postcolitic), and rectal nociception was assessed by measuring the behavioral response during CRD. Healthy rats were administered with sodium hydrogen sulfide (NaHS) (as a source of H(2)S), L-cysteine, or vehicle. In a second model, we investigated nociception to CRD in rats recovering from a chemically induced acute colitis. We found that CBS and CSE are expressed in the colon and spinal cord. Treating rats with NaHS resulted in a dose-dependent attenuation of CRD-induced nociception with the maximal effect at 60 micromol/kg (p < 0.05). Administration of L-cysteine, a CSE/CBS substrate, reduced rectal sensitivity to CRD (p < 0.05). NaHS-induced antinociception was reversed by glibenclamide, a ATP-sensitive K(+) (K(ATP)) channel inhibitor, and N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric-oxide (NO) synthase inhibitor. The antinociceptive effect of NaHS was maintained during the resolution of colon inflammation induced by intrarectal administration of a chemical irritant. In summary, these data show that H(2)S inhibits nociception induced by CRD in both healthy and postcolitic rats. This effect is mediated by K(ATP) channels and NO. H(2)S-releasing drugs might be beneficial in treating painful intestinal disorders.

The aim of this study was to develop a new behavioral pain test based on the evaluation of cognitive capacity impairments in rats with colitis and to determine the impact of different acute analgesic treatments. Colitis was induced in rats by an enema containing 2,4,6-trinitrobenzen sulfonic acid. Visual non-selective, non-sustained attentional level was assessed by a new behavioral testing procedure. Animals were familiarized on three consecutive days with an open field containing four small, similar, familiar objects. On the day of testing, one of the objects was randomly replaced by a new one. Attentional level was determined by the ability of the rat to perceive this small modification to its familiar environment. The effect of morphine, acetaminophen, aspirin or ibuprofen treatment was assessed on testing day and compared with that observed during a Von Frey test to assess referred tactile hypersensitivity of the skin of the lower back. Rats with colitis had decreased attentional level but no change in their locomotor activity, interest in the environment or memory encoding. Morphine (1 mg/kg, s.c. and 10 microg/rat, i.t.) and acetaminophen (200 mg/kg, p.o.) had a beneficial effect on attentional level and on referred tactile hypersensitivity. Testing for the latter showed that aspirin and ibuprofen (400 mg/kg, p.o.) were ineffective. The decrease in visual non-selective, non-sustained attention induced by chronic inflammatory painful state can be relieved by effective analgesic treatments. This finding could lead to the development of a new behavioral test to assess spontaneous pain in chronic painful subjects.

Background: Stressful events in the early period of life (for example, maternal deprivation) have been shown to modify adult immune and gastrointestinal tract functions. The present study aimed to establish whether maternal deprivation affects colonic epithelial barrier and the development of an experimental colitis in adult rats., Methods: Male Wistar rat pups were separated during postnatal days 2-14 or left undisturbed with their dam. At 12 weeks of age, we assessed colonic paracellular permeability, bacterial translocation, myeloperoxidase (MPO) activity, mucosal mast cell density, cytokine (interleukin (IL)-1 beta, IL-2, IL-4, IL-10, and interferon gamma (IFN-gamma)) mRNA expression, and macroscopic damage. Total gut permeability, MPO activity, and macroscopic damage were also assessed four days after intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS)., Results: Maternal deprivation triggered a significant increase in colonic permeability associated with bacterial translocation into the mesenteric lymph nodes, liver, and spleen. These alterations were associated with some macroscopic damage and an increase in colonic MPO activity, mucosal mast cell density, and cytokine mRNA expression. Intracolonic infusion of TNBS induced a significantly higher inflammatory reaction in separated animals, as judged by enhanced MPO colonic levels, total gut permeability, and macroscopic lesions., Conclusions: Maternal deprivation promotes long term alterations in the colonic epithelial barrier associated with an exaggerated immune response to an external immune stimulus. This suggests a role for early psychological factors in the regulation of colonic mucosal barrier in later life.

In this study, we investigated the effects of three neonatal conditions on adult corticosterone (CORT) levels, acoustic startle responses (ASRs), and vulnerability to colitis induced by dextran sulfate sodium (DSS) and how these early manipulations might interact with a brief stress exposure in adulthood on the same measures. Infant animals were subjected daily to either 180-min maternal separation [prolonged maternal separation (LMS)], 10-min maternal separation [brief maternal separation (BMS)], or nonhandling (NH) conditions during postnatal days 1-14. As adults, half of the animals were exposed to a series of 10 uncontrollable foot shocks. Animals were tested for CORT levels prior to and 10 days following shock/nonshock procedures before being tested for ASRs. Finally, all animals were exposed to 4% DSS in their drinking water for 6 days. LMS animals showed enhanced vulnerability to DSS-induced colitis when previously exposed to shock and enhanced stress reactivity responses as shown by elevated startle and CORT levels. Among the nonshocked animals, NH animals showed most colonic damage. Taken together, the results support previous findings suggesting that BMS has a protective effect on adult stress exposure. Additionally, BMS protects the animals from chemically induced colitis. The NH condition has clearly an effect on sensitizing mucosal response to DSS exposure.

The generation of transgenic mice that lack or overexpress genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is widely used in mice. Here we describe a novel model, chemical stimulation of the colon, which we have developed in mice. Mice of either sex were injected i.v. with 30 mg/kg Evan's Blue for subsequent determination of plasma extravasation. For behavioural testing, they were placed on a raised grid and 50 microl of saline, mustard oil (0.25-2.5%) or capsaicin (0.03-0.3%) was administered by inserting a fine cannula into the colon via the anus. Visceral pain-related behaviours (licking abdomen, stretching, contractions of abdomen etc) were counted for 20 min. Before intracolonic administration, and 20 min after, the frequency of withdrawal responses to the application of von Frey probes to the abdomen was tested. The colon was removed post-mortem and the Evan's Blue content measured. Mustard oil and capsaicin administration evoked dose-dependent visceral pain behaviours, referred hyperalgesia (significant increase in responses to von Frey hairs) and colon plasma extravasation. The peak behavioural responses were evoked by 0.1% capsaicin and by 1% mustard oil respectively. The nociceptive behavioural responses were dose-dependently reversed by morphine (ED50 = 1.9 +/- 1 mg/kg s.c.). We conclude that this model represents a useful tool both for phenotyping mutant mice and for classical pharmacology since information on visceral pain, referred hyperalgesia and colon inflammation can all obtained from the same animal.

The case is discussed of a 74-year-old patient hospitalised with acute colitis, who newly developed headache, fever, and mental status changes on the 14th day after admission. The course of the disease was characterised by rapid progression with loss of consciousness and the development of extensive brain oedema, despite broad-spectrum antibiotic therapy. The patient died on the 17th of hospitalisation.

A new rat model was established up to evaluate the antinociceptive effect of compounds in visceral pain. The test consisted in measuring the performance of rats in an aversive light stimulus avoidance experimental device. Rats with TNBS-induced colitis had a lower number of total active lever pressings and did not discriminate the active lever from the inactive one. Morphine (1 mg/kg, s.c.) and CI-977 (0.001 mg/kg, s.c.) treatment restored the level of pressing activity of animals and their ability to discriminate the active lever from the inactive one. Naloxone treatment antagonized the improvement of performance produced by morphine. The results obtained indicate that this behavioral paradigm may be used to evaluate the antinociceptive potential of compounds.

We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day 1 and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis.

The objective of this study was to examine the antinociceptive effects of peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of inflammatory bowel disease produced by intracolonic instillation of trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine) and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80) on responses of pelvic nerve afferent fibers innervating the colon were also tested. In the behavioral study, systemic injections of morphine and both kappa-ORAs dose-dependently inhibited the visceromotor response to colorectal distension in rats with uninflamed or inflamed colons. The inhibitory effects of kappa-ORAs, but not morphine, were significantly greater in rats with colons inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg) of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC 80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs dose-dependently inhibited responses of pelvic nerve afferent fibers with significantly greater potency in the inflamed colon. Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid receptors in colonic inflammation.

Experimental colitis was induced in rats by intrarectal infusion of trinitrobenzenesulfonic acid and ethanol. Colitis was accompanied by a large suppression of food intake of 3 days duration. The reduction of food intake was effected through a reduction of meal size, with no change in meal frequency. Those same rats demonstrating approximately 70%-80% suppression of daily food intake showed no reduction of sham feeding. These data indicate that malaise alone is inadequate to explain the suppression of food intake associated with acute colitis. Rather, the data suggest that the suppression of eating results from an exaggerated postprandial satiety signal elaborated during the period of acute inflammation, an interpretation consistent with the demonstration of a slowed rate of gastric emptying in association with the colitis.

Acute colitis occurring in patients suffering from psychiatric illnesses is believed to be linked to the intake of psychotropes. From 1983 to 1989, the authors observed, in three Hepato-gastroenterology units, 10 cases of acute colitis in patients suffering from serious psychiatric disorders, most of them inpatients of mental hospitals. The detailed study of 7 of these cases emphasized a certain number of common features: there was no previous history of digestive disease, the psychiatric illness was serious and longstanding, acute colitis was severe, and there was no recurrence during clinical and endoscopic follow-up averaging 4.3 years. Of these 7 patients, 2 were not taking psychotropes at the time of colitis or after, 2 had discontinued their treatment for a few days, and 2 had not stopped taking psychotropes. One patient died. The short-term and long-term evolution in these cases was not influenced by the intake or not of psychotropes. The pathogeny of this colitis is yet to be determined: infection is the most likely origin.

This is a critical review of 16 studies reporting a relationship between Crohn's disease and psychological variables. The studies reviewed indicate a relationship between the psychological variables of stressful life events, personality characteristics, and psychopathology and the onset and/or exacerbation of Crohn's symptoms. Personality characteristics such as depression, anxiety, and dependency are frequently reported as are the occurrence of stressful life events and the presence of psychopathology. The nature of the relationship is not explained by the research to date; however, the findings summarized in this report indicate that additional investigation into this association is warranted. A plan for such research is suggested.

Experience shows that infections in the region of the gastrointestinal tract are apparently not very common causes of traffic accidents. In particular, impairment by the disease itself including treatment with its effects and side effects must be considered. Also the patient's own assessment of his condition is extremely meaningful and must not be disregarded at the consultation. Furthermore the length and circumstances of the journey and consideration of the age of the patient and other disease conditions are important.