Visceral Sensitivity Research Articles

Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota.

Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce visceral hypersensitivity in PI-IBS mice. Assessment of intestinal visceral sensitivity using the abdominal withdrawal reflex (CRD). 16S ribosomal RNA (16S rRNA) sequencing to profile the gut microbiome community. GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.

Role of Inflammation and Motility Disorders in the Development, Course and Consequences of Functional Gastrointestinal and Biliary Tract Diseases (Literature Review and Expert Panel Resolution)

Aim: to present the results of the Expert Panel with a discussion of modern concepts of the pathogenesis of functional gastrointestinal diseases and the possibilities of multitarget therapy with trimebutine. Key points. Low-grade inflammation can be considered as a morphological substrate of functional diseases with an increase in activated mastocytes and eosinophils, T-helpers 2 and T-helpers 17 in the gastrointestinal mucosa. In the development in the content of visceral hypersensitivity, the functional connection between mastocytes and TRPV1-positive sensory endings of the vagus nerve is of great importance. Proinflammatory cytokines and matrix metalloproteinases can enter the systemic circulation, provoking the development of systemic manifestations. Increased levels of proinflammatory cytokines are supported by altered intestinal permeability and microbiota. Functional diseases are believed to modify the symptoms and course of concomitant organic diseases of the gastrointestinal tract (for example, functional diseases of the biliary tract may contribute to the development of cholelithiasis, pancreatitis). The peripheral μ-, κ- and δ-receptor agonist trimebutine (Trimedat®) regulates the production of enterohormones, modulates motility throughout the gastrointestinal tract and normalizes visceral sensitivity. The effectiveness of trimebutine in the treatment of functional disorders has been shown in various studies. Trimebutine helps reduce the production of proinflammatory cytokines, including interleukin-6. Conclusion. In the treatment of functional diseases of the gastrointestinal tract, trimebutine can be considered as a multitarget agent, since the drug helps to normalize motility, reduces the degree of visceral hypersensitivity, exhibits anti-inflammatory and neuroregenerative effects, and can also increase the effectiveness of treatment of concomitant diseases.

A Synbiotic Combining Chitin-Glucan and Lactobacillus acidophilus NCFM Induces a Colonic Molecular Signature Soothing Intestinal Pain and Inflammation in an Animal Model of IBS.

Chitin-glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1β, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes.

Positive affect longitudinally buffers the negative effect of health anxiety on gastrointestinal symptoms.

People with significant health anxiety may experience brain-gut dysregulation, leading to increased visceral sensitivity and greater gastrointestinal (GI) symptoms. Positive affect (PA), on the other hand, may serve as a protective characteristic, buffering the negative impact of health anxiety on GI symptoms. This study investigated interrelationships between health anxiety, PA, and GI symptoms. Longitudinal data were collected on health anxiety, PA, and GI symptoms via an online survey from 861 adults at two timepoints, 4 weeks apart. Regression models were conducted to examine the moderating effect of PA at baseline on future GI symptoms. Greater health anxiety at baseline predicted GI symptoms at follow-up, whereas higher levels of PA predicted reduced GI symptoms at follow-up. Post hoc testing revealed that PA significantly moderated the relationship between health anxiety and GI symptoms over time, such that higher levels of PA attenuated the effect of health anxiety on belly pain, nausea and vomiting, and reflux at follow-up. This study provides preliminary evidence PA may buffer the negative impact of health anxiety on GI symptoms. Future studies should explore whether the promotion of PA through interventions similarly attenuates health related anxiety's impact on GI symptoms.

Exploring the Therapeutic Potential of Sodium Butyrate in Irritable Bowel Syndrome. A Literature Review

Introduction and purpose Irritable bowel syndrome (IBS) is a prevalent digestive condition marked by symptoms like abdominal discomfort, bloating, and irregular bowel movements. Sodium butyrate, a short-chain fatty acid recognized for its anti-inflammatory effects and benefits to gut health, has gained attention as a potential treatment for IBS. This review seeks to assess the existing research on the effectiveness and safety of sodium butyrate in managing IBS. Material and methods This work was based on a review of the literature available on PubMed. We included studies corresponding to the keywords: sodium butyrate, irritable bowel disease, butyric acid. Results Research has shown that sodium butyrate supplementation significantly alleviated abdominal pain, bloating, and overall IBS symptoms compared to a placebo. Notable improvements were seen in both visceral pain sensitivity and gut permeability. Furthermore, combining sodium butyrate with probiotics may offer additional benefits. The treatment was generally well-tolerated, easily accessible, and cost-effective. Conclusion Sodium butyrate shows promise as a therapeutic option for managing IBS, with studies indicating its effectiveness in reducing symptoms and enhancing gut health. However, more extensive, well-structured clinical trials are required to validate these results, determine optimal dosage, and assess long-term safety and efficacy.

Activation of EphrinB2/EphB2 signaling in the spine cord alters glia-neuron interactions in mice with visceral hyperalgesia following maternal separation.

Sress early in life has been linked to visceral hyperalgesia and associated functional gastrointestinal disorders. In a mouse model of visceral hyperalgesia, we investigated whether the EphB2 receptor and its EphrinB2 ligand in spinal cord contribute to dysregulation of glia-neuron interactions. An established mouse model of stress due to maternal separation (MS). Pups were separated from their mothers for 14 days during early development, then analyzed several weeks later in terms of visceral sensitivity based on the abdominal withdrawal reflex score and in terms of expression of c-fos, EphrinB2, EphB2, and phosphorylated MAP kinases (ERK, p38, JNK). Visceral hyperalgesia due to MS upregulated EphB2, EphrinB2 and c-fos in the spinal cord, and c-fos levels positively correlated with those of EphB2 and EphrinB2. Spinal astrocytes, microglia, and neurons showed upregulation of EphB2, EphrinB2 and phosphorylated MAP kinases. Blocking EphrinB2/EphB2 signaling in MS mice reduced visceral sensitivity, activation of neurons and glia, and phosphorylation of NMDA receptor. Activating EphrinB2/EphB2 signaling in unstressed mice induced visceral hyperalgesia, upregulation of c-fos, and activation of NMDA receptor similar to maternal separation. The stress of MS during early development may lead to visceral hyperalgesia by upregulating EphrinB2/EphB2 in the spinal cord and thereby altering neuron-glia interactions.

Further validation of the visceral sensitivity index: Psychometric properties and utility for predicting disordered eating in a diverse university sample

Gastrointestinal (GI) visceral sensitivity (i.e., anxiety/worry over GI sensations) may be a key maintaining factor for disordered eating; however, it is unknown whether GI visceral sensitivity predicts the range of disordered eating behaviors in nonclinical samples. The current preregistered study aimed to replicate previous construct validity findings of the Visceral Sensitivity Index (VSI; i.e., factor structure, convergent and discriminant validity) and examine its criterion-related validity for predicting a range of disordered eating attitudes and behaviors in a diverse undergraduate sample. A total of 591 university students were retained in the final analytic sample (53 % women; 23 % Hispanic [Any Race], 10 % Asian, 9 % Black) and completed the VSI, disordered eating, and additional validity measures. A confirmatory factor analysis tested the factor structure of the VSI, and correlations were used to examine convergent and discriminant validity. Hierarchical regressions and t-tests were used to examine criterion-related validity. Results replicated previous construct validity findings in a diverse undergraduate sample. Exploratory analyses supported invariance of the VSI across gender and the VSI discriminated between individuals at high- versus low-risk for an eating disorder and predicted a range of disordered eating attitudes (e.g., body dissatisfaction) and behaviors (e.g., restricting, binge eating, purging, compulsive exercise). GI-specific anxiety appears to be transdiagnostic across disordered eating behaviors and relevant across the spectrum of disordered eating severity. Future work may include developing transdiagnostic models of GI visceral sensitivity in disordered eating and investigating inclusion of the VSI in university screening efforts.

Impact of mechanical barrier damage and interleukin-17 on symptoms in patients with post-infectious irritable bowel syndrome.

Aims/Background The pathogenesis of irritable bowel syndrome encompasses various factors, including abnormal gastrointestinal motility, heightened visceral sensitivity, dysfunction in the brain-gut axis, psychological influences, and disturbances in the intestinal flora. These factors manifest primarily as persistent or intermittent abdominal pain, diarrhoea, alterations in bowel habits, or changes in stool characteristics. In our investigation, we delve into the repercussions of mechanical barrier damage and immune dysfunction on symptoms among patients with post-infectious irritable bowel syndrome. Methods This study recruited a total of 20 healthy controls and 49 patients diagnosed with irritable bowel syndrome. Among the irritable bowel syndrome patients, we categorised them into two groups based on the ROME IV diagnostic criteria: the post-infectious irritable bowel syndrome group (n=23) and the non-post-infectious irritable bowel syndrome group (n=26). To compare clinical features, we utilised the Gastrointestinal Symptom Rating Scale, Self-Rating Depression Scale, and Self-Rating Anxiety Scale. Furthermore, we employed various techniques including haematoxylin and eosin (HE) staining, electron microscopy, Enzyme-linked Immunosorbent Assay, and flow cytometry to assess changes in immune cells, immune factors, inflammatory biomarkers, and intestinal barrier function. Results Under haematoxylin and eosin staining, post-infectious irritable bowel syndrome patients demonstrated increased neutrophils and plasma cells compared to the control group. Additionally, electron microscopy revealed ultrastructural changes such as the widening of the epithelial cell gap in the intestinal mucosa among post-infectious irritable bowel syndrome patients. Comparatively, the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale scores were significantly elevated in the post-infectious irritable bowel syndrome group in contrast to both the control group and the non- post-infectious irritable bowel syndrome group (p < 0.05). Moreover, post-infectious irritable bowel syndrome patients exhibited a notably higher neutrophil-to-lymphocyte ratio compared to the control group (p < 0.05). Furthermore, the levels of interleukin-17 (IL-17) were elevated in post-infectious irritable bowel syndrome patients compared to the control group (p < 0.05). Additionally, the post-infectious irritable bowel syndrome group displayed a higher percentage of T helper 17 (Th17) cells compared to both the control and non-post-infectious irritable bowel syndrome groups (p < 0.05). Conclusion Acute gastrointestinal infection can disrupt the balance of intestinal flora, leading to dysbiosis. This dysbiosis can trigger the release of pro-inflammatory factors, including interleukin-17, which contributes to the impairment of the intestinal mucosal barrier. Consequently, this sets the stage for the development of long-lasting, mild chronic intestinal inflammation, ultimately culminating in the onset of post-infectious irritable bowel syndrome. Furthermore, within the framework of the gut-brain axis interaction, anxiety and depression may exacerbate intestinal inflammation in post-infectious irritable bowel syndrome patients. This interaction can perpetuate and prolong clinical symptoms in individuals with post-infectious irritable bowel syndrome, further complicating the management of the condition.

Interoceptive Processing in Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGIDs) are characterized by chronic gastrointestinal symptoms in the absence of overt pathology and affect a significant percentage of the worldwide population. They are commonly accompanied by co-morbid psychiatric symptomatology and are associated with significant suffering and great healthcare services utilization. There is growing evidence that dysregulation of the gut-brain axis and disturbances in the processing of afferent interoceptive signals lie at the heart of these disorders. In this context, the aim of the current review was to detect and critically review original articles focusing on the role of interoception in the pathophysiology of FGIDs. Our search yielded 38 relevant studies. FGID patients displayed increased visceral sensitivity, enhanced attention to gastrointestinal interoceptive cues, and greater emotional arousal when coping with gut-derived sensations. Neuroimaging studies have shown significant structural and functional changes in regions of the interoceptive network, while molecular and genetic studies have revealed significant associations between interoceptive signaling and deficits in excitatory neurotransmission, altered endocrine and immune physiological pathways, and aberrant expression of transient receptor potential channel genes. Finally, there were emerging data suggesting that interoception-based interventions may reduce physical symptoms and improve quality of life and should be integrated into FGID clinical management practices.

Effects of chronic unpredictable mild stress on gut sensation and function in male mice

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice’s behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

VISCERAL SENSITIVITY INDEX (VSI-IT): Italian Adaptation and Validation.

The Visceral Sensitivity Index (VSI) represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with irritable bowel syndrome (IBS) and chronic inflammatory bowel diseases (IBD)-such as ulcerative colitis and Crohn's disease. However, an Italian version of the instrument is not yet available for the Italian-speaking population. This study utilized a national sample of 500 individuals divided into four groups: (a) patients with Crohn's disease, (b) patients with ulcerative colitis, (c) patients with IBS, and (d) healthy controls (individuals without any diagnoses) to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, this research applied a questionnaire and the VSI through an online format to 500 participants. Confirmatory Factor Analysis (CFA) revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach's α = 0.949) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with interoceptive awareness, type of disease, and gastrointestinal symptom severity, confirming its role in enhancing the understanding and management of IBD and IBS in Italy.

Dectin-1 induces TRPV1 sensitization and contributes to visceral hypersensitivity of irritable bowel syndrome in male mice.

Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.

Probiotics plus vitamin D in irritable bowel syndrome: a prospective multicentric non-interventional study.

Patients with irritable bowel syndrome (IBS) experience recurrent symptoms and anxiety disorders that significantly impact their quality of life (QoL). The aim of the study was to assess in daily practice the benefit of the combination of three probiotic strains (Lactobacillus plantarum CETC 7484 and CETC 7485; Pediococcus acidilactici CECT 7483) plus vitamin D in patients with diarrhea-predominant IBS (IBS-D) or IBS with mixed bowel movements (IBS-M). This was a prospective, multicenter, non-interventional study in adult patients with IBS-D or IBS-M (Rome IV criteria) followed by private-practice gastroenterologists. Patients received daily one sachet of a combination of probiotics (3×109 CFU) and vitamin D (10 μg) for 42 days. The primary endpoint was the responder rate at D42 (≥50% and/or ≥100-point decrease of IBS-Severity Scoring System; IBS-SSS). Gut-related anxiety was measured with the Visceral Sensitivity Index (VSI). The full analysis set population included 246 patients (mean age, 51.2±15.4 years; women, 73.2%; IBS-D, 56.1%; IBS-M, 43.9%). At D42, among the 89 patients with evaluable data, the responder rate was 62.9% with a mean decrease of IBS-SSS of 146.6±125.9 (P<0.0001). Changes of IBS-SSS were significantly correlated with changes of IBS-QoL (r=-0.78; P<0.0001), HAD-anxiety (r=0.46; P<0.0001), HAD-depression (r=0.61; P<0.001) and VSI (r=0.74; P<0.0001). These real-life results are in line with a previous randomized clinical trial demonstrating the benefits of this combination in IBS-D and IBS-M. Symptom relief was associated with improvement of IBS-QoL, anxiety, depression and specifically gut-related anxiety.

The role of the gut microbiome in disorders of gut–brain interaction

Disorders of Gut‐Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large‐scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite‐host interactions, offering exciting possibilities for the future of treatment of DGBI.

The GABAergic pathway from anterior cingulate cortex to lateral hypothalamus area regulates irritable bowel syndrome in mice and its underlying mechanism.

Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS-like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro-Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma-aminobutyric acid-producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC-LHA GABAergic pathway. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5-hydroxytryptamine (5-HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS-like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS-like symptoms. The chemogenetic activation of ACC-LHA GABAergic neurons elicited anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC-LHA GABAergic neurons alleviated anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC-LHA GABAergic pathway in modulating anxiety-like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS-like symptoms.

A novel animal model for understanding secondary traumatic stress and visceral pain in male rats.

Empathetic relationships and the social transference of behaviours have been shown to occur in humans, and more recently through the development of rodent models, where both fear and pain phenotypes develop in observer animals. Clinically, observing traumatic events can induce 'trauma and stressor-related disorders' as defined in the DSM 5. These disorders are often comorbid with pain and gastrointestinal disturbances; however, our understanding of how gastrointestinal - or visceral - pain can be vicariously transmitted is lacking. Visceral pain originates from the internal organs, and despite its widespread prevalence, remains poorly understood. We established an observation paradigm to assess the impact of witnessing visceral pain. We utilised colorectal distension (CRD) to induce visceral pain behaviours in a stimulus rodent while the observer rodent observed. Twenty four hours post-observation, the observer rodent's visceral sensitivity was assessed using CRD. The observer rodents were found to have significant hyperalgesia as determined by lower visceral pain threshold and higher number of total pain behaviours compared with controls. The behaviours of the observer animals during the observation were found to be correlated with the behaviours of the stimulus animal employed. We found that observer animals had hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis, highlighted by reduced corticosterone at 90 minutes post-CRD. Using c-Fos immunohistochemistry we showed that observer animals also had increased activation of the anterior cingulate cortex, and decreased activation of the paraventricular nucleus, compared with controls. These results suggest that witnessing another animal in pain produces a behavioural phenotype and impacts the brain-gut axis.

Treating disorders of brain-gut interaction with multidisciplinary integrated care. Moving towards a new standard of care.

Disorders of brain-gut interaction (DGBI) are highly prevalent in our community with a negative burden on the quality of life and function. Symptoms are frequently food-induced, and psychological disorders are commonly co-morbid and contribute greatly to symptom severity and healthcare utilization, which can complicate management. Pathophysiological contributors to the development and maintenance of DGBI are best appreciated within the biopsychosocial model of illness. Established treatments include medical therapies targeting gastrointestinal physiology, luminal microbiota or visceral sensitivity, dietary treatments including dietary optimization and specific therapeutic diets such as a low-FODMAP diet, and psychological interventions. The traditional "medical model" of care, driven predominantly by doctors, poorly serves sufferers of DBGI, with research indicating that a multidisciplinary, integrated-care approach produces better outcomes. This narrative review explores the current evidence for multidisciplinary care and provides the best practice recommendations for physicians and healthcare systems managing such patients.

Tong-Xie-Yao-Fang strengthens intestinal feedback control of bile acid synthesis to ameliorate irritable bowel syndrome by enhancing bile salt hydrolase-expressing microbiota

Ethnopharmacological relevanceA herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used to treat irritable bowel syndrome (IBS), modern pharmacological evidence supports that the formula efficacy is associated with altered gut microbiota. Yet, the mechanistic role of gut microbiota in the therapy of TXYF remains unclear. We previously clarified that gut microbiota-dysregulated bile acid (BA) metabolism contribute to the pathogenesis of IBS, deriving a hypothesis that microbiota-BA metabolic axis might be a potential target of TXYF. Aim of the studyWe aim to investigate a new gut microbiota-mediated mechanism underlying anti-IBS efficacy of TXYF. Materials and methodsWe established an IBS rat model with a combination of stressors, compared the herbal efficacy in models undergone gut bacterial manipulations, also examined BA metabolism-related microbiota, metabolites, genes and proteins by 16S rRNA gene sequencing, targeted metabolomics, qPCR and multiplex immunofluorescence staining. ResultsWe observed that TXYF attenuated visceral hyperalgesia and diarrhea in IBS rats but not in those underwent gut bacteria depletion. Transferring gut microbiota from TXYF-treated donors also decreased visceral sensitivity and slightly relief diarrhea-like behaviors in IBS recipient rats. Fecal 16S rRNA gene sequencing revealed that TXYF modulated microbial β-diversity and taxonomic structure of IBS rats, with a significant increase in relative abundance of bile salt hydrolase (BSH)-expressing Bacteroidaceae. qPCR and culturing data validated that TXYF had a promotive effect on the growth and BSH activity of Bacteroides species. TXYF-reshaped microbiota upregulated the expression of intestinal Fgf15, a feedback signal to control BA synthesis in the liver. As a result, the BA synthetic and excretory levels in IBS rats were decreased by TXYF, so as that colonic BA membrane receptor Tgr5 sensing and its mediated Calcitonin gene-related peptide (Cgrp)-positive neuronal response were attenuated. ConclusionThis study poses a new microbiota-driven therapeutic action for TXYF, highlighting the potential of developing new anti-IBS strategies from the herbal formula targeting BSH-expressing gut bacteria.

Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats.

Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate-induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism-related proteins, and acid-sensitive ion channel 3/extracellular signal-regulated kinase (ASIC3/ERK) pathway-related molecules. PF treatment not only attenuated compound diphenoxylate-induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5-hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.

Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome

BackgroundDiarrheal irritable bowel syndrome (IBS-D), characterized primarily by the presence of diarrhea and abdominal pain, is a clinical manifestation resulting from a multitude of causative factors. Furthermore, Sishen Wan (SSW) has demonstrated efficacy in treating IBS-D. Nevertheless, its mechanism of action remains unclear. MethodsA model of IBS-D was induced by a diet containing 45 % lactose and chronic unpredictable mild stress. Additionally, the impact of SSW was assessed by measuring body weight, visceral sensitivity, defecation parameters, intestinal transport velocity, intestinal neurotransmitter levels, immunohistochemistry, and transmission electron microscopy analysis. Immunofluorescent staining was used to detect the expression of Mucin 2 (MUC2) and Occludin in the colon. Western blotting was used to detect changes in proteins related to tight junction (TJ), autophagy, and endoplasmic reticulum (ER) stress in the colon. Finally, 16S rRNA amplicon sequencing was used to monitor the alteration of gut microbiota after SSW treatment. ResultsOur study revealed that SSW administration resulted in reduced visceral sensitivity, improved defecation parameters, decreased intestinal transport velocity, and reduced intestinal permeability in IBS-D mice. Furthermore, SSW promotes the secretion of colonic mucus by enhancing autophagy and inhibiting ER stress. SSW treatment caused remodeling of the gut microbiome by increasing the abundance of Blautia, Muribaculum and Ruminococcus torques group. ConclusionSSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.