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

BACKGROUND: Diarrheal 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. METHODS: A 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. RESULTS: Our 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. CONCLUSION: SSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.

Development and Validation of a High-Performance Liquid Chromatography Method to Quantify Marker Compounds in Lysimachia vulgaris var. davurica and Its Effects in Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.

Prevalence of Isolated Irritable Bowel Syndrome Among Adults in the Kingdom of Bahrain.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common gastrointestinal disorder encountered in clinical practice. In this study, we estimated the prevalence of isolated IBS and its associated demographic factors among the adult population in the Kingdom of Bahrain. METHODS: A cross-sectional study was conducted targeting adults in Bahrain aged 18 years and above. Individuals with a prior diagnosis of any bowel ailment were excluded. Data was acquired via a self-administered questionnaire. IBS-specific questions were derived from the validated Rome IV diagnostic questionnaire for adults. The scoring methodology inherent to this questionnaire was used for the diagnosis of IBS. The data collection process remained anonymous. Data was compiled using Excel spreadsheets, and the Statistical Package for Social Sciences (SPSS) was employed for analytical purposes. Associations between IBS and demographical or behavioral characteristics were explored using the Chi-square test. RESULTS: The prevalence of isolated IBS, adopting the Rome IV criteria, was 156 (18.3%) and IBS-M (mixed) type was 40 (38.1%) of these. IBS was predominantly higher among females compared to males (340 vs 235; 22.6% vs 11.9%). The majority of IBS cases (121, 21%) were in the 41-50 age group. A statistically significant association has been demonstrated between IBS and GERD using Pearson's chi-squared test (p-value = 0.000). Similarly, it was linked to indigestion (p-value = 0.00). CONCLUSIONS: Although the percentage appeared to be significantly higher than the global prevalence of 4% (using Rome IV criteria), our findings were equivalent to the reports conducted in the Middle East region. Integrating holistic patient assessments, including quality of life metrics, along with anxiety, depression, and vitamin D deficiency, will further enhance the understanding of IBS in Bahrain and its impact on the patients and the health services utilization.

Integrative Approaches to Managing Gut Health.

PURPOSE OF REVIEW: To summarize key integrative approaches to managing common gastrointestinal conditions. RECENT FINDINGS: Lifestyle interventions like diet, exercise, and stress reduction impact the gut microbiome and gastrointestinal symptoms. Evidence supports mind-body therapies, herbs, certain supplements, and other modalities as complimentary approaches, when appropriate, for common conditions like irritable bowel syndrome or gastroesophageal reflux disease. An integrative approach optimizes both conventional treatments and incorporates lifestyle modifications, complimentary modalities, and the doctor-patient relationship.

Unmet needs of drugs for irritable bowel syndrome and inflammatory bowel diseases: interest of vagus nerve stimulation and hypnosis.

The gut and the brain communicate bidirectionally through the autonomic nervous system. The vagus nerve is a key component of this gut-brain axis, and has numerous properties such as anti-inflammatory, antinociceptive, anti-depressive effects. A perturbation of this gut-brain communication is involved in the pathogeny of functional digestive disorders, such as irritable bowel syndrome, and inflammatory bowel diseases. Stress plays a role in the pathogeny of these diseases, which are biopsychosocial models. There are presently unmet needs of pharmacological treatments of these chronic debilitating diseases. Treatments are not devoid of side effects, cost-effective, do not cure the diseases, can lose effects over time, thus explaining the poor satisfaction of patients, their lack of compliance, and their interest for non-drug therapies. The gut-brain axis can be targeted for therapeutic purposes in irritable bowel syndrome and inflammatory bowel disease through non-drug therapies, such as hypnosis and vagus nerve stimulation, opening up possibilities for responding to patient expectations.

Osteopathic manipulative treatment for chronic inflammatory diseases.

Chronic inflammatory diseases (CIDs) are debilitating and potentially lethal illnesses that affect a large proportion of the global population. Osteopathic manipulative treatment (OMT) is a manual therapy technique developed and performed by osteopathic physicians that facilitates the body's innate healing processes. Therefore, OMT may prove a beneficial anti-inflammatory modality useful in the management and treatment of CIDs. This work aims to objectively evaluate the therapeutic benefits of OMT in patients with various CIDs. In this review, a structured literature search was performed. The included studies involving asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, ankylosing spondylitis, and peripheral arterial disease were selected for this work. Various OMT modalities, including lymphatic, still, counterstain, and muscle energy techniques, were utilized. Control treatments included sham techniques, routine care, or no treatment. OMT utilization led to variable patient outcomes in individuals with pathologies linked to CID.

A multi-omics study reveals the therapeutic effect of Linderae Radix water extract on irritable bowel syndrome (IBS-D).

ETHNOPHARMACOLOGICAL RELEVANCE: Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. AIM OF THE STUDY: While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. MATERIALS AND METHODS: 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. RESULTS: LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. CONCLUSIONS: This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D.

A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.

Prebiotics and Probiotics for Gastrointestinal Disorders.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Effect of moxibustion on colonic low-grade inflammatory response in rats with diarrhea-predominant irritable bowel syndrome based on mast cell degranulation. / åŸºäºŽè‚¥å¤§ç»†èƒžè„±é¢—ç²’æŽ¢è®¨è‰¾ç¸å¯¹è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ ç»“è‚ ä½Žåº¦ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of moxibustion on colonic mast cell degranulation and inflammatory factor expression in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and explore the potential mechanism of moxibustion in treating IBS-D. METHODS: Forty-five rat pups born from 5 healthy SPF-grade pregnant SD rats, with 8 rats were randomly selected as the normal group. The remaining 37 rats were intervened with maternal separation, acetic acid enema, and chronic restraint stress to establish the IBS-D model. The successfully modeled 32 rats were then randomly assigned to a model group, a ketotifen group, a moxibustion group, and a moxibustion-medication group, with 8 rats in each group. The rats in the ketotifen group were intervened with intragastric administration of ketotifen solution (10 mL/kg); the rats in the moxibustion group were intervened with suspended moxibustion on bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the moxibustion-medication group were intervened with suspended moxibustion combined with intragastric administration of ketotifen solution. All interventions were administered once daily for 7 consecutive days. The diarrhea rate and minimum volume threshold of abdominal withdrawal reflex (AWR) were calculated before and after modeling, as well as after intervention. After intervention, colonic tissue morphology was observed using HE staining; colonic mucosal ultrastructure was examined by scanning electron microscopy; colonic mast cell ultrastructure was observed using transmission electron microscopy; mast cell degranulation was assessed by toluidine blue staining; serum and colonic levels of histamine, interleukin (IL)-1ß, IL-6, IL-1α, trypsin-like enzyme, and protease-activated receptor 2 (PAR-2) were measured by ELISA; the Western blot and real-time quantitative PCR were employed to evaluate the protein and mRNA expression of colonic IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2; the immunofluorescence was used to detect the positive expression of histamine, IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colonic tissue. RESULTS: Compared to the normal group, the rats in the model group exhibited extensive infiltration of inflammatory cells in colonic tissue, severe damage to the colonic mucosa, disordered arrangement of villi, reduced electron density, and a significant decrease in granule quantity within mast cells. The diarrhea rate and mast cell degranulation rate were increased (P<0.01), AWR minimum volume threshold was decreased (P<0.01); the serum and colonic levels of histamine, IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were elevated (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all elevated (P<0.01). Compared to the model group, the rats in the ketotifen group, the moxibustion group, and the moxibustion-medication group exhibited significantly reduced infiltration of inflammatory cells in colonic tissue, relatively intact colonic mucosa, orderly arranged villi, increased electron density, and an augmented number of mast cell granules; the diarrhea rate and mast cell degranulation rate were decreased (P<0.01), and AWR minimum volume threshold was increased (P<0.01); the serum and colonic levels of histamine, IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 were reduced (P<0.01); the positive expression of histamine, as well as protein, mRNA and positive expression of IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 in the colon were all decreased (P<0.01). Compared to the ketotifen group, the moxibustion group showed decreased serum levels of histamine, IL-6, and trypsin-like enzyme (P<0.01, P<0.05), as well as reduced colonic levels of IL-1ß and IL-6 (P<0.01, P<0.05); the protein expression of colonic IL-1ß, IL-1α, and PAR-2 was reduced (P<0.05), and the positive expression of colonic IL-1ß and trypsin-like enzyme was reduced (P<0.01, P<0.05). Compared to both the ketotifen group and the moxibustion group, the moxibustion-medication group exhibited decreased diarrhea rate and mast cell degranulation rate (P<0.01), an increased AWR minimum volume threshold (P<0.01), reduced serum and colonic levels of histamine, IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01), decreased protein expression of colonic IL-1ß, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), reduced mRNA and positive expression of colonic IL-1ß, IL-6, IL-1α, trypsin-like enzyme, and PAR-2 (P<0.01, P<0.05), and decreased positive expression of colonic histamine (P<0.01). CONCLUSIONS: Moxibustion on "Tianshu" (ST 25) and "Shangjuxu" (ST 37) might inhibit low-grade inflammatory reactions in the colon of IBS-D model rats. The mechanism may be related to the inhibition of histamine and trypsin-like enzyme secreted by mast cell, thereby reducing the expression of related inflammatory factors.

Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM).

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

Electroacupuncture Improving Intestinal Barrier Function in Rats with Irritable Bowel Syndrome Through Regulating Aquaporins.

BACKGROUND: Intestinal mucosal barrier dysfunction plays a crucial role in the pathogenesis of irritable bowel syndrome with diarrhea (IBS-D). In order to explore the mechanism of electroacupuncture (EA) treatment on intestinal mucosal barrier, this study observed the effect of EA on aquaporins (AQPs), tight junctions (TJs), NF-κB pathway and the gut microbiota in IBS-D rats. METHODS: The IBS-D model was established by acetic acid enema combined with chronic restraint method. The effects of EA on the treatment of IBS-D were examined by the abdominal withdrawal reflex score, Bristol's fecal character score, fecal water content, small intestine propulsion rate and HE staining. AQPs, TJs and inflammation-related molecular mechanisms were explored. The fecal samples were applied for 16S rRNA sequencing to assess the effect of EA intervention to the intestinal bacterial abundance. RESULTS: EA reduced intestinal sensitization, restored intestinal motility and improved inflammatory cell infiltration. Furthermore, EA improved intestinal inflammation and flora environment significantly, inhibited NF-κB signaling and inflammatory factors (IL-1ß and TNF-α). It can also increase the gene and protein expression of AQPs (AQP1, AQP3, and AQP8) and the gene levels of TJs (ZO-1 and Occludin). CONCLUSION: EA has an inhibitory effect on the NF-κB signaling pathway, and regulates the proteins of AQP1, AQP3, AQP8, and TJs to restore the balance of water metabolism and intestinal permeability in IBS-D, which also restored the function of the intestinal mucosa by regulating the intestinal flora.

Efficacy and safety of peppermint oil for the treatment in Japanese patients with irritable bowel syndrome: a prospective, open-label, and single-arm study.

BACKGROUND: In Europe, an herbal medicine containing peppermint oil is widely used in patients with irritable bowel syndrome (IBS). In Japan, however, no clinical evidence for peppermint oil in IBS has been established, and it has not been approved as a drug for IBS. Accordingly, we conducted a clinical study to confirm the efficacy and safety of peppermint oil (ZO-Y60) in Japanese patients with IBS. METHODS: The study was a multi-center, open-label, single-arm, phase 3 trial in Japanese outpatients with IBS aged 17-60 years and diagnosed according to the Rome III criteria. The subjects were treated with an oral capsule of ZO-Y60 three times a day before meals, for four weeks. The efficacy of ZO-Y60 was evaluated using the patient's global assessment (PtGA), IBS symptom severity score, stool frequency score, stool form score, and physician's global assessment (PGA). The safety of ZO-Y60 was also assessed. RESULTS: Sixty-nine subjects were treated with ZO-Y60. During the four-week administration of ZO-Y60, the improvement rate of the PtGA was 71.6% (48/67) in week 2 and 85.1% (57/67) in week 4. It was also suggested that ZO-Y60 is effective against any type of IBS (IBS with constipation, IBS with diarrhea, and mixed/unsubtyped IBS). The improvement rate of the PGA was 73.1% (49/67) in week 2 and 85.1% (57/67) in week 4, also confirming the efficacy of ZO-Y60. Adverse events were observed in 14 subjects (20.3%), however, none of these adverse events were categorized as serious. CONCLUSION: The efficacy of treatment was confirmed, subjective symptoms were improved, as was observed in previous clinical studies of ZO-Y60 conducted outside of Japan. All adverse reactions were previously known and were non-serious. These findings suggest that peppermint oil may be effective in the Japanese population and that it has an acceptable safety profile. TRIAL REGISTRATION: JAPIC Clinical Trials Information number: JapicCTI-121727 https://jrct.niph.go.jp/en-latest-detail/jRCT1080221685 . Registration date: 2012-01-10.

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity.

BACKGROUND: Chronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non-clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms. METHODS: We assessed acute and long-term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity. KEY RESULTS: Chronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively. Long-term, but not acute, oral administration of Menthacarin (60 mg kg-1 day-1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation. CONCLUSIONS & INFERENCES: The present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.

Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome.

Limited treatment options have been shown to alter the natural course of constipation-predominant irritable bowel syndrome (IBS-C). Therefore, safer and more effective approaches are urgently needed. We investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of IBS-C. In the current study, C57BL/6 mice were randomly divided into normal control, IBS-C model control, sham-electrostimulation (sham-ES), taVNS, and drug treatment groups. The effects of taVNS on fecal pellet number, fecal water content, and gastrointestinal transit were evaluated in IBS-C model mice. We assessed the effect of taVNS on visceral hypersensitivity using the colorectal distention test. 16S rRNA sequencing was used to analyze the fecal microbiota of the experimental groups. First, we found that taVNS increased fecal pellet number, fecal water content, and gastrointestinal transit in IBS-C model mice compared with the sham-ES group. Second, taVNS significantly decreased the abdominal withdrawal reflex (AWR) score compared with the sham-ES group, thus relieving visceral hyperalgesia. Third, the gut microbiota outcomes showed that taVNS restored Lactobacillus abundance while increasing Bifidobacterium probiotic abundance at the genus level. Notably, taVNS increased the number of c-kit-positive interstitial cells of Cajal (ICC) in the myenteric plexus region in IBS-C mice compared with the sham-ES group. Therefore, our study indicated that taVNS effectively ameliorated IBS-C in the gut microbiota and ICC.

Nutraceuticals and Pain Disorders of the Gut-Brain Interaction in Infants and Children: A Narrative Review and Practical Insights.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through a search of the literature in Pubmed and Medline updated to October 2023 focused on the effect of nutraceuticals in infantile colic, functional abdominal pain, and irritable bowel syndrome in children and adolescents. Significant reductions in colic episodes and crying time were reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to a placebo, in children with functional abdominal pain or irritable bowel syndrome, a significant reduction in pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, and in one study on corn fiber cookies, partial hydrolyzed guar gum, a specific multiple herbal extract (STW-5), or vitamin D supplementation. To date, there is moderate-certainty evidence with a weak grade of recommendation on Lactobacillus reuteri DSM 17938 (108 CFU/day) in reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 × 109 CFU twice daily) in reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove the efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Treatment of functional bowel disorders in an integrative medicine clinic resulting in improved digestive tract symptoms.

Background and Aim: Functional bowel disorders (FBDs), including irritable bowel syndrome (IBS) and others, are conditions without a physically identifiable etiology that, as a result, are difficult to treat. Alternatives to traditional medical interventions are needed because IBS patients require more of physician time and higher healthcare spending. The goal of this study was to determine the efficacy of alternative lifestyle interventions for patients with FBDs seen in an integrative medicine (IM) clinic at an academic medical center. Methods: We performed a retrospective chart review to determine whether patients with FBDs had improvement in symptoms following predominantly nutrition-based IM interventions that included recommendations for dietary supplements and elimination diets. We measured symptoms before and after intervention (average time between measurements 8.75 months) using a medical symptoms questionnaire (MSQ) commonly used to quantify symptom change in IM clinics. Results: Digestive tract symptoms, as measured by the MSQ, improved significantly in patients (n = 57) with FBDs following IM intervention. The MSQ Digestive Tract subtotal for FBD patients decreased from 10.2 (SD, 5.4) to 7.2 (SD, 5.2) (P < 0.001) after IM intervention. Conclusions: Patients in an IM clinic had improved digestive tract symptoms scores following IM intervention. Because nutrition-based interventions were the primary intervention recommended by IM providers, primary care physicians and gastroenterologists may wish to consider referring FBD patients to registered dietitian-nutritionists (RDNs) skilled in implementing elimination diets.

Moxibustion ameliorates visceral hypersensitivity by regulating hypothalamus-spinal cord-colon axis in rats with irritable bowel syndrome with diarrhea. / 基于下丘脑-脊髓-ç»“è‚ è½´æŽ¢è®¨è‰¾ç¸æ”¹å–„è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ å† è„é«˜æ•æ„Ÿçš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe the effect of moxibustion intervention on the hypothalamus-spinal cord-colon axis of rats with irritable bowel syndrome with diarrhea (IBS-D) and explore the mechanism of moxibustion in improving visceral hypersensitivity in rats with IBS-D. METHODS: A total of 36 SD rats were randomly divided into normal, model, and moxibustion groups, with 12 rats in each group. The IBS-D model was established by maternal separation + acetic acid stimulation + chronic restraint. Rats of the moxibustion group received bilateral moxibustion on "Tianshu" (ST25) and "Shangjuxu" (ST37) for 15 min, once a day for 7 consecutive days. The body weight, loose stool rate, and minimum threshold volume of abdominal withdrawal reflex (AWR) were measured before and after moxibustion intervention, respectively. The histopathological changes in the colon tissue were observed after HE staining. The number of colonic mucosal mast cells (MCs) was measured by toluidine blue staining. The activation of MCs was determined by tryptase positive expression level and examined by immunohistochemical staining. The content, protein and mRNA expression levels and positive expression levels of corticotropin releasing factor (CRF), substance P (SP), and calcitonin gene-related peptide (CGRP) in the hypothalamus, spinal cord and colon tissues were measured by ELISA, Western blot, real-time fluorescent quantitative PCR and immunofluorescence staining, respectively. RESULTS: Compared with the normal group, the loose stool rate was increased (P<0.01)；the body weight and minimum threshold volume of AWR were decreased (P<0.01)；the inflammatory infiltration of colon tissues was obvious；the number of MCs and positive expression level of tryptase in the colon tissue were increased (P<0.01)；the contents, positive expression le-vels, protein and mRNA expression levels of CRF, SP and CGRP in the hypothalamus, spinal cord and colon tissues were increased (P<0.01, P<0.05) in the model group. After the intervention, compared with the model group, all these indicators showed opposite trends (P<0.01, P<0.05) in the moxibustion group. CONCLUSIONS: Moxibustion can improve visceral hypersensitivity in rats with IBS-D, and its mechanism may be related to regulating the hypothalamic-spinal-colon axis to reduce the release of CRF, SP and CGRP, and thus to inhibite MC in colon tissue.