Inflammation and Overlap of Irritable Bowel Syndrome and Functional Dyspepsia

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) and account for a large proportion of consulting patients. These 2 disorders overlap with each other frequently. The pathogenesis of IBS or FD is complicated and multi-factors related, in which infectious or non-infectious inflammation and local or systemic immune response play significant roles. There are few studies focusing on the mechanism of inflammation in patients with overlap syndrome of irritable bowel syndrome and functional dyspepsia (IBS-FD). This review focuses on current advances about the role of inflammation in the pathogenesis of IBS and FD and the possible mechanism of inflammation in IBS-FD.

Inflammation and Overlap of Irritable Bowel Syndrome and Functional Dyspepsia

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) and account for a large proportion of consulting patients. These 2 disorders overlap with each other frequently. The pathogenesis of IBS or FD is complicated and multi-factors related, in which infectious or non-infectious inflammation and local or systemic immune response play significant roles. There are few studies focusing on the mechanism of inflammation in patients with overlap syndrome of irritable bowel syndrome and functional dyspepsia (IBS-FD). This review focuses on current advances about the role of inflammation in the pathogenesis of IBS and FD and the possible mechanism of inflammation in IBS-FD.

Treatment of diabetic gastroparesis: current status / 中华全科医师杂志

Diabetic gastroparesis (DGP) is a common complication in patients with diabetes mellitus of long duration, presenting with recurrent nausea, vomiting, postprandial fullness and early satiety caused by delayed gastric emptying. The treatments of DGP include dietary therapy, nutritional support, glycemic control, use of prokinetic and antiemetic agents. This review focuses on current status of the drug treatment and the progress of new agents of DGF under the preclinical and clinical trials.

Advances in Study on Pathogenesis of Irritable Bowel Syndrome / 胃肠病学

The pathophysiological process of irritable bowel syndrome (IBS) is complex. Recent studies showed that alteration in gut microbiota, damage of intestinal mucosal barrier and increase of mucosal permeability due to inflammation, diet and stress, as well as abnormalities of enteric nervous system in both function and morphology play important roles in the development of IBS. In this article, the advances in studies on above mentioned pathogenic mechanisms of IBS were briefly summarized.

Depression and Structural Factors Are Associated With Symptoms in Patients of Irritable Bowel Syndrome With Diarrhea

Background/Aims@#A strong correlation between depression and irritable bowel syndrome with diarrhea (IBS-D) has been identified. The aim of this study is to identify the correlations among depression, structural factors, gastrointestinal (GI) and extra-GI symptoms, and efficacy of neuromodulators in patients with IBS-D. @*Methods@#Patients meeting the Rome III Diagnostic Criteria for IBS-D were enrolled. The intestinal symptoms and psychological states were evaluated using IBS-specific symptom questionnaires and Hamilton Depression Rating Scale. @*Results@#In total, 410 patients with IBS-D were enrolled, 28.8% (118/410) had comorbid depression. Patients with depression did not readily experience improvement in abdominal pain/discomfort after defecation, and had a higher prevalence of passing mucus, overlapping functional dyspepsia, and extra-GI symptoms. The structural factor “mental disorders” significantly correlated with main bowel symptom score and degree of pre-defecation abdominal pain/discomfort. No structural factor significantly correlated with bowel movements or stool form. Patients who had passing mucus, overlapping functional dyspepsia and extra-GI painful symptoms have higher score of “anxiety/somatization.” Patients with sexual dysfunction have higher score of “retardation symptoms.” In total, 28.3% of patients with IBS-D were prescribed neuromodulators. Baseline scores of “anxiety/somatization” and “retardation symptoms” positively correlated with improvement of diarrhea after paroxetine, and “sleep disturbances” positively correlated with improvement of abdominal pain/discomfort and diarrhea after mirtazapine. @*Conclusions@#Comorbid depression and higher scores of structural factors might aggravate GI and extra-GI symptoms other than bowel movements and stool form. Structural factors of Hamilton Depression Rating Scale correlated with efficacy of paroxetine and mirtazapine in patients with IBS-D.

The 470th case: recurrent vomiting / 中华内科杂志

Patients with cyclic vomiting syndrome usually have comorbid psychological disorders,the trigger and aggravating factors of gastrointestinal symptoms.It may decrease the quality of life and the response to the conventional therapies,bring the patients to seek medical care frequently and perform unnecessary examinations,result in the waste of medical resources.We reported a 20-year-old woman with complaint of recurrent vomiting since infant,and less response to symptomatic and supportive treatment.Her vomiting relieved with antidepressant after consultation with gastroenterological specialist and psychologist.Physicians should pay more attention to recognize the comorbid psychological disorders in patients with functional gastrointestinal disorders (FGIDs),including cyclic vomiting syndrome.It is important to refer the patients with refractory symptoms to the psychologists for further professional evaluation and antidepressants.

Esophageal Motor Dysfunctions in Gastroesophageal Reflux Disease and Therapeutic Perspectives

Gastroesophageal reflux disease (GERD) is a very common disease, and the prevalence in the general population has recently increased. GERD is a chronic relapsing disease associated with motility disorders of the upper gastrointestinal tract. Several factors are implicated in GERD, including hypotensive lower esophageal sphincter, frequent transient lower esophageal sphincter relaxation, esophageal hypersensitivity, reduced resistance of the esophageal mucosa against the refluxed contents, ineffective esophageal motility, abnormal bolus transport, deficits initiating secondary peristalsis, abnormal response to multiple rapid swallowing, and hiatal hernia. One or more of these mechanisms result in the reflux of stomach contents into the esophagus, delayed clearance of the refluxate, and the development of symptoms and/or complications. New techniques, such as 24-hour pH and multichannel intraluminal impedance monitoring, multichannel intraluminal impedance and esophageal manometry, high-resolution manometry, 3-dimensional high-resolution manometry, enoscopic functional luminal imaging probe, and 24-hour dynamic esophageal manometry, provide more information on esophageal motility and have clarified the pathophysiology of GERD. Proton pump inhibitors remain the preferred pharmaceutical option to treat GERD. The ideal target of GERD treatment is to restore esophageal motility and reconstruct the anti-reflux mechanism. This review focuses on current advances in esophageal motor dysfunction in patients with GERD and the influence of these developments on GERD treatment.

Second Asian Consensus on Irritable Bowel Syndrome

BACKGROUND/AIMS: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. METHODS: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. RESULTS: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. CONCLUSIONS: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

Regional Brain Activity During Rest and Gastric Water Load in Subtypes of Functional Dyspepsia: A Preliminary Brain Functional Magnetic Resonance Imaging Study

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.

Impact of comorbid psychological disorders on intestinal symptoms in patients with irritable bowel syndrome with diarrhea / 中华消化杂志

Objective To investigate the clinical symptoms and mental state of patients with irritable bowel syndrome with diarrhea (IBS-D ) , and to analyze the characteristics of psychological disorders in patients with IBS-D and their impacts on intestinal symptoms .Methods From July 2009 to June 2012 ,patients met Rome Ⅲ criteria of IBS-D were consecutively enrolled at Peking Union Medical College Hospital .The symptoms of IBS were investigated by IBS symptoms questionnaire and mental state were evaluated by Hamilton anxiety scale (HAMA ) and Hamilton depression scale (HAMD ) . The differences in intestinal symptoms between patients with comorbid psychological disorders and without psychological disorders were compared .And the correlation between the scores of HAMA ,HAMD and intestinal symptoms were analyzed . Two independent sample t-tests ,chi square test and Fisher exact probability were performed for statistical analysis .Spearman rank correlation was used for correlation analysis .Results A total of 231 patients with IBS-D were enrolled .There were 133 males and 98 females with an age of (42 .8 ± 11 .1) years old and a disease course of (4 .5 years (8 .0 years)) .The HAMA and HAMD scores were 17 .00 ± 7 .12 and 14 .05 ± 6 .00 ,respectively ,and 72 .29％ (167/231) patients had comorbid psychological disorders ,32 .90％ (76/231 ) patients had moderate to severe anxiety and/or depression ,mainly had anxiety .The proportion of patients with ordinary abdominal pain or discomfort and the proportion of moderate to severe abdominal pain or discomfort in patients with psychological disorders were higher than those of patients without psychological disorders (53 .29％ , 89/167 vs . 34 .37％ , 22/64;49 .44％ ,44/89 vs .18 .18％ ,4/22) ,and the differences were statistically significant (χ2=6 .634 and 7 .002 , P=0 .010 and 0 .009) .In patients with comorbid psychological disorders ,more patients had frequent onset of abdominal pain or discomfort ,less achieved completely improvement after defecation , and often accompanied with defecation related symptoms .The HAMD score was positively correlated with the onset frequency of IBS (r=0 .172 ,P=0 .009) ,and the HAMA score was positively correlated with the degree of abdominal pain or discomfort before defecation (r=0 .134 , P= 0 .042) .The HAMA and HAMD scores were negatively correlated with the improvement degree of abdominal pain or discomfort after defecation (r= -0 .215 , P=0 .001 ;r= -0 .251 , P<0 .01) ,and were positively correlated with waiting time for symptoms improvement (r=0 .175 , P=0 .008;r=0 .219 , P= 0 .001) .Conclusion Most IBS-D patients have comorbid psychological disorders , anxiety and/or depression greatly impact the intestinal symptoms of patients with IBS .

Consistency between symptoms and colorectoanal function tests in elderly patients with functional constipation / 中华全科医师杂志

Objective To analyze the consistency between constipated symptoms and the parameters of gastrointestinal transit time (GITT),anorectal manometry (ARM) in elderly patients with functional constipation.Methods Total 111 patients (54 males and 57 females) with an average age of (70.2±6.5) years,who met Rome Ⅲ criteria of functional constipation were enrolled from June 2010 to October 2012.After enrollment,patients took two-week diary,recording the spontaneous bowel movements per week,stool type of Bristol Stool Form,the frequency and severity of defecation straining,sensation of anorectal obstruction,manual maneuvers and sensation of incomplete evacuation.The GITT and ARM tests were performed,and the consistency between symptoms and test results were analyzed.Results Patients with symptoms of slow transit,defecation disorder and mixed symptoms were 19.8％ (22/111),16.2％ (18/ 111) and 59.5％ (66/111) respectively;and 4.5％ (5/111) patients had scattered symptoms.Based on results of GITT,slow transit subtype,defecation disorder subtype and mixed subtype were 54.1％ (59/109),1.8％ (2/ 109) and 29.4％ (32/109) respectively;and 14.7％ (16/109) patients were with normal transit time.ARM results showed that 38.0％ (41/109) of patients had dyssynergic defecation.The percentage of slow transit in GITT test showed no significant difference between patients with slow transit symptoms and mixed symptoms [50.0％ (11/22)vs.57.9％(33/57),x2=0.401,P=0.527].The consistency of predominant symptom with GITI subtype was low (κ=-0.013).The percentage of dyssynergic defecation detected with ARM showed no significant difference between patients with defecation disorder-predominant symptom and with mixed symptom [23.1％ (6/24)vs.38.2％ (21/55),x2=1.813,P=0.178].The consistency of defecation disorderpredominant symptom with dyssynergic defecation in ARM was low (κ=-0.019).Conclusion The mixed subtype symptoms are the most common presentations of elderly patients with functional constipation,and the consistency of predominant constipated symptoms with GITI,ARM test results is poor.

Understanding and Management of Irritable Bowel Syndrome-like Symptoms Coexisting With Quiescent Inflammatory Bowel Disease in A Comprehensive Perspective / 胃肠病学

Symptoms compatible with irritable bowel syndrome (IBS) such as abdominal pain and diarrhea may co exist in approximately one-third of patients with quiescent inflammatory bowel disease (IBD),so called IBS-like symptoms.These symptoms present as a clinical dilemma for management of IBD and diminish the patients' quality of life remarkably.IBS-like symptoms raise much concern in the research field of IBD in recent years.In this article,the latest research progress focusing on the prevalence,pathogenesis and management of IBS-like symptoms coexisting with quiescent IBD was reviewed.

The efficacy and safety of testa triticum tricum purif in treatment of functional constipation in the late middle-aged and elderly patients: a multicenter randomized controlled clinical trial / 中华内科杂志

Objective To evaluate the efficacy and safety of testa triticum tricum purif for the treatment of functional constipatiofi(FC) in the late middle-aged and elderly patients.Methods This study was designed as a multicenter randomized controlled trial.Patients who met Rome Ⅲ diagnostic criteria of FC were enrolled,with age between 55-85 years old.Those with organic diseases were excluded.The patients were randomly allocated to receive testa triticum tricum purif (3.5 g bid) or polyethylene glycol 4000 powder (PEG4000,10g bid) for 8 weeks,followed by single dose of maintenance therapy for 4 weeks.Follow-up visits were at 4 and 12 weeks after treatment discontinuation.The independent investigators in each center evaluated the constipation symptoms scores.The primary endpoints included rates of significant improvement,improvement and overall improvement at the end of 2,4 and 8 weeks of therapy,which were calculated by the reduction of symptom scores ≥ 75 ％,50％-74％,≥ 25 ％ respectively.Results A total of 127 FC subjects were enrolled from 3 centers,and 122 cases valid for final analysis.The mean age was (69.4 ± 6.9) years old,including 62 cases in testa triticum tricum purif group and 60 cases in PEG4000 group.The demographic data,constipated symptoms scores and proportion of FC subtypes at baseline were comparable.The rates of significant improvement,improvement and overall improvement in testa triticum tricum purif and PEG4000 groups at the end of 2,4 and 8 weeks were 37.70％ (23/61) vs 59.32％(35/59) (P=0.018),57.38％ (35/61)vs74.14％ (43/58) (P=0.054),and64.41％ (38/59)vs 79.31％ (46/58) (P =0.073) respectively.Testa triticum tricum purif therapy significantly improved the proportion of spontaneous bowel movement (SBM) ≥ 3 times/week from 43.55％ (27/62) to 80.33％ (49/61),83.61％ (51/61) and 93.22％ (55/59) at 2,4,and 8 weeks respectively (all P＜0.01),which were comparable with PEG4000 group (all P ＞ 0.05).The proportion of normalized stool forms in study group was significant higher than that of control group at the end of 8 weeks [86.44％ (51/59) vs 67.24％ (39/58),P =0.014].Only one patient complained mild abdominal distension during testa triticum tricum purif therapy.Conclusions The efficacy of testa triticum tricum purif for the treatment of FC in late middle-aged and older patients is comparable with osmotic laxatives PEG4000,which has significant effect on normalization of fecal forms and reliable safety.

Clinical characteristics of chronic intestinal pseudo-obstruction : an analysis of 43 cases / 中华全科医师杂志

Objective To analyze the clinical characteristics of chronic intestinal pseudoobstruction (CIPO).Methods Clinical data of 43 patients with CIPO admitted in Peking Union Medical College Hospital from January 2012 to December 2016 were retrospectively reviewed.The clinical manifestations,laboratory examinations,images,treatment and prognosis of CIPO patients were analyzed.Results There were 14 males and 29 females with an mean age of (41.9 ± 16.1) years.Among 43 patients,32 were admitted in Gastroenterology Department,6 in General Medicine Department and 5 in Rheumatology Department.Twenty two cases were primary CIPO and 21 cases were secondary.The main clinical manifestations were abdominal distension (93.0％),abdominal pain (67.4％),vomiting (67.4％),diarrhea (46.5％) and constipation (41.9％).All 43 patients had decreased body weight and body mass index (BMI);23.3％ (10/43) patients were complicated with anxiety and depression.53.5％ (23/43) patients presented anemia and 55.8％ (24/43) patients presented hypoalbuminemia.All patients with CIPO underwent abdominal X-ray,which showed intestinal obstruction;but there was no evidence of mechanical obstruction.The average length of hospital stay was (28.4 ± 13.9) d.Twenty three cases underwent gastric decompression;28 cases (65.1％) received parenteral nutrition,and 21 cases (48.8％) received enteral nutrition;and 9 abdominal operations were performed in 8 patients.Conclusion When clinical symptoms of intestinal obstruction appear without mechanical cause,CIPO should be considered and secondary factors should be screened.Unnecessary surgery should be avoided in CIPO patients.

Pros and cons of probiotics in immunocompromised individuals / 中华全科医师杂志

Probiotics as intestinal flora regulators are increasingly applied in clinical practice;however,the administration of probiotics in immunocompromised individuals is rarely reported.This article is aimed to review the benefits and risks of probiotics in immunocompromised individuals,such as HIV-infected individuals and patients with malignant tumors.The research evidence shows that probiotics can reduce the occurrence of different types of diarrhea,regulate the intestinal immune status and decrease the incidence of complications in immunocompromised patients.Randomized controlled clinical trials have shown that the risk of adverse events is not significantly increased in immunocompromised patients compared to those with intact immune status and the probiotics-related infections are only presented in case reports.

Symptomatic characteristics and factors related to severity of irritable bowel syndrome / 中华全科医师杂志

Objective To analyze symptomatic characteristics and the factors related to severity of irritable bowel syndrome (IBS).Methods Total 516 IBS patients met Rome Ⅲ criteria were enrolled in the study from June 2009 to February 2016.A questionnaire survey was conducted in face-to-face manner,including intestinal and extra-intestinal symptoms,sleeping and psychological status.Severity of IBS was determined by symptom scores.Results Among 516 patients,there were 135 cases with mild symptoms (26.2％),267 with moderate symptoms (51.7％) and 114 with severe symptoms (22.1％).Periumbilical pain/discomfort associated with defecation was a common symptom location (34.6％,178/516),however,53.3％ (275/516) patients also reported having abdominal pain/discomfort during non-defecation period.In IBS patients,51.2％ (264/516) were coexisted with gastroesophageal reflux disease (GERD),59.1％ (305/516) with functional dyspepsia (FD),and 46.9％ (242/516) with depression.The prevalence of ordinary abdominal pain/discomfort [57.0％ (217/381) vs.43.0％ (58/135),x2 =7.841],sensation of incomplete defecation[74.5％ (284/381)vs.61.5％ (83/135),x2 =8.277] and coexisted GERD[54.1％ (206/381) vs.43.0％(58/135),x2 =4.920],FD[64.0％(244/381)vs.45.2％ (61/135),x2 =14.664],headache[50.7％ (193/381)vs.38.5％ (52/135),x2 =5.889] and depression[52.2％ (199/ 381)vs.31.9％ (43/135),x2 =16.623] in patients with moderate to severe symptoms were significantly higher than that in patients with mild symptoms (all P ＜ 0.05).The predictors to moderate-severe IBS symptoms were coexisted FD (OR =1.798,95％ CI:1.162-2.783,P =0.010) and depression (OR =1.696,95％ CI:1.043-2.759,P =0.014).Conclusion The symptoms of IBS patients are various,and patients coexisted with FD and depression are more likely to have more severe symptoms.

Characteristics and clinical significance of sera anti-enteric neuronal antibodies in patients with irritable bowel syndrome with diarrhea / 基础医学与临床

Objective To detect the sera anti-enteric neuronal antibodies ( AENA ) in irritable bowel syndrome with diarrhea ( IBS-D) patients and analyzed its correlation with IBS-D symptoms to explore the potential roles of AENA in the pathogenesis of IBS.Methods IBS-D patients diagnosed with RomeⅢdiagnostic criteria were en-rolled in this study.The sera of healthy subjects were used as controls.Indirect immunofluorescence ( IIF) was used to detect the sera AENA with the substrate of ileal submucosal plexus of guinea pig .The immune reactivity ( IR) stains were read in blinded method .The bowel symptoms of patients with positive AENA were compared to thatwithnegativeandweeklypositiveantibodies.Results 1)Atotalof127IBS-Dpatientswereenrolledinthis study.The positive rate of sera AENA was 85.8%in IBS-D patients, and 7.0%in healthy controls.Among 109 IBS-D patients with positive IIF reactivity , 23.6%present with strong positive , 43.3% with positive and 18.9%with weakly positive stain .The IR patterns included cytoplasm staining , nucleus staining , cytoplasms and nuclei staining , nuclear membrane staining , cytoplasm and nuclear membrane staining .Six positive sera of healthy control showed cytoplasm staining to substrate neurons .2 ) More patients of IBS-D with positive IR had higher intestinal symptoms scores (>10 scores, 58.8%vs 38.1%), frequent abdominal pain in non-defecation period (91.7%vs 60.0%) , and severe abdominal pain/discomfort before defecation ( 24.7% vs 9.5%) comparing to those with negative and weekly positive IR of AENA;IBS-D patients with positive IR of AENA are more commonly associated with urgency comparing to those with negative IR in IIF (57.1%vs 87.3 ) .Conclusions AENA may play a role in the pathogenesis of IBS , and is a potential biomarker of IBS-D.

Application of Roman IIII( criteria in the diagnosis of chronic constipation / 中华胃肠外科杂志

In Rome IIII( diagnostic system, disorders associated with chronic constipation include functional constipation, opioid-induced constipation, irritable bowel syndrome with predominant constipation and functional defecation disorders, each disorder has the relative characteristics of clinical manifestations and underlying pathophysiology. Rome IIII( committee modified the diagnostic criteria based on current research achievements, and recommended to make the diagnosis of functional constipation disorders with minimal laboratory test and with indications for colonoscopy and pathophysiological tests. Understanding the clinical manifestations and pathophysiology of functional constipation disorders are helpful for clinicians to apply the Rome diagnostic criteria and improve the accuracy of diagnosis and treatment for the patients with chronic constipation.

Clinical characteristics of functional constipation in the elderly:symptoms, pathophysiology and treatment / 中华老年医学杂志

The clinical symptoms of functional constipation in the elderly are more unique which represents as over concern about their bowel movement,excessive straining and worse feelings to the constipation.The intestinal physiological function declining with age,reductions of enteric neurons and interstitial cells of Cajal,neuronal degeneration and injured contractibility of intestinal smooth cells are enrolled in the pathogenesis of functional constipation.More attention should be paid to drug interactions and adverse effects in clinical practice due to more underlying disease and concomitant medication in the elderly.

Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.