Psychological factors may affect the quality of life in irritable bowel syndrome patients more than the gut itself? A multicenter cross-sectional study.

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL. Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics. Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation (r = -0.398), fatigue (r = -0.266), and weakness (r = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety (r = -0.564) and depression (r = -0.411) were significantly negatively correlated with QOL (P < 0.001). Psychological factors showed the strongest impact (ß' = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor (ß' = -0.421). Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized.

Characteristics and Risk Factors of Functional Dyspepsia Fulfilling the Rome IV Criteria Overlapping With Gastroesophageal Reflux Disease, Irritable Bowel Syndrome, and Functional Constipation in South China.

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

The Short-Term Efficacy of Bifidobacterium Quadruple Viable Tablet in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: Potentially Mediated by Metabolism Rather Than Diversity Regulation.

INTRODUCTION: The therapeutic effect of probiotics for irritable bowel syndrome (IBS) was controversial. This study aims to evaluate the short-term efficacy of Bifidobacterium quadruple viable tablet in patients with diarrhea-predominant IBS and explore factors associated with response to probiotics. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was performed in 15 hospitals. A total of 290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week follow-up. The primary outcome was the response rate. It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously. RESULTS: After 4-week continuous administration, the response rates of the probiotics and the placebo were 67.59% and 36.55%, respectively ( P < 0.001). In the probiotics, those with higher abdominal pain scores (2.674 [1.139-6.279]) were more likely to respond, but responders in placebo had lower Hamilton Depression Scale score (0.162 [0.060-0.439]), lower Hamilton Anxiety Scale score (0.335 [0.148-0.755]), and higher degree of bloating (2.718 [1.217-6.074]). Although the diversity of the microbiota was not significantly changed by probiotics, the abundance of bacteria producing short-chain fatty acids (SCFAs), including Butyricimonas ( P = 0.048), Pseudobutyrivibrio ( P = 0.005), Barnesiella ( P = 0.020), and Sutterella ( P = 0.020), and the concentration of SCFAs including butyric acid ( P = 0.010), valeric acid ( P = 0.019), and caproic acid ( P = 0.046) in feces increased. DISCUSSION: A Bifidobacterium quadruple viable tablet had a significant short-term efficacy for the treatment of diarrhea-predominant IBS and was more effective in patients with higher abdominal pain scores. This kind of probiotics could improve the abundance of several bacteria producing SCFAs and the concentration of fecal SCFAs compared with placebos.

Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization.

Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with Fusobacterium nucleatum (F. nucleatum, Fn) infection. In this study, we explored the role of F. nucleatum in the CRC metastasis. Our results showed that the abundance of F. nucleatum was enriched in the feces and tumors of patients with CRC and tended to increase in stage IV compared to stage I in patients with metastatic CRC. Tumor-derived CCL20 activated by F. nucleatum not only increases CRC metastasis, but also participates in the reprograming of the tumor microenvironment. F. nucleatum promoted macrophage infiltration through CCL20 activation and simultaneously induced M2 macrophage polarization, enhancing the metastasis of CRC. In addition, we identified using database prediction and luciferase activity hat miR-1322, a candidate regulatory micro-RNA, could bind to CCL20 directly. F. nucleatum infection decreased the expression of miR-1322 by activating the NF-κB signaling pathway in CRC cells. In conclusion, F. nucleatum promotes CRC metastasis through the miR-1322/CCL20 axis and M2 polarization.

Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet compared with traditional dietary advice for diarrhea-predominant irritable bowel syndrome: a parallel-group, randomized controlled trial with analysis of clinical and microbiological factors associated with patient outcomes.

BACKGROUND: The efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions consuming a non-Western diet are unclear. OBJECTIVES: We aimed to determine the efficacy of an LFD compared with TDA for the treatment of IBS-D in Chinese patients and to investigate the factors associated with favorable outcomes. METHODS: One hundred and eight Chinese IBS-D patients (Rome III criteria) were randomly assigned to an LFD or TDA. The primary endpoint was a ≥50-point reduction in the IBS Severity Scoring System at 3 wk. Fecal samples collected before and after the dietary intervention were assessed for changes in SCFAs and microbiota profiles. A logistic regression model was used to identify predictors of outcomes. RESULTS: Among the 100 patients who completed the study, the primary endpoint was met in a similar number of LFD (30 of 51, 59%) and TDA (26 of 49, 53%) patients (∆6%; 95% CI: -13%, 24%). Patients in the LFD group achieved earlier symptomatic improvement in stool frequency and excessive wind than those following TDA. LFD reduced carbohydrate-fermenting bacteria such as Bifidobacterium and Bacteroides, and decreased saccharolytic fermentation activity. This was associated with symptomatic improvement in the responders. High saccharolytic fermentation activity at baseline was associated with a higher symptom burden (P = 0.01) and a favorable therapeutic response to the LFD (log OR: 4.9; 95% CI: -0.1, 9.9; P = 0.05). CONCLUSIONS: An LFD and TDA each reduced symptoms in Chinese IBS-D patients; however, the LFD achieved earlier symptomatic improvements in stool frequency and excessive wind. The therapeutic effect of the LFD was associated with changes in the fecal microbiota and the fecal fermentation index. At baseline, the presence of severe symptoms and microbial metabolic dysbiosis characterized by high saccharolytic capability predicted favorable outcomes to LFD intervention.This trial was registered at clinicaltrials.gov as NCT03304041.

The Diagnosis Performance of the TCM Syndromes of Irritable Bowel Syndrome by Gastroenterologists Based on Modified Simple Criteria Compared to TCM Practitioners: A Prospective, Multicenter Preliminary Study.

PURPOSE: Traditional Chinese medicine (TCM) including Chinese patent medicine has been widely used to treat irritable bowel syndrome (IBS). Syndrome differentiation is the essence of TCM. However, the diagnostic ability of gastroenterologists to detect TCM syndromes in IBS in China remains unknown. The aim of this study was to investigate the ability of gastroenterologists to diagnose the TCM syndromes of IBS based on modified simple criteria compared with TCM practitioners. METHODS: Patients meeting the Rome III criteria for IBS-D or IBS-C were recruited from six tertiary referral centers between January 2016 and December 2017. After learning the diagnosis criteria of the TCM syndromes in IBS, gastroenterologists first diagnosed the syndromes of the enrolled patients. Subsequently, the patients were diagnosed by TCM practitioners. The rate of agreement between the gastroenterologists and TCM practitioners was analyzed. In addition, demographic data and the distribution of TCM syndrome types in IBS were also analyzed. RESULTS: A total of 178 patients (93 males and 85 females), including 131 patients with IBS-D and 47 patients with IBS-C, were enrolled in this study. The rate of agreement of the syndrome diagnosis between the gastroenterologists and TCM practitioners was 84.3%. The diagnosis consistency rates among IBS-D patients and IBS-C patients were 87.0% and 76.5%, respectively. The most common TCM syndrome type in IBS-D patients was liver depression and spleen deficiency syndrome (27.5%), followed by spleen-yang deficiency syndrome (19.8%). Dryness and heat in intestine syndrome was the most common TCM syndrome in IBS-C patients (57.4%). CONCLUSIONS: Gastroenterologists had good diagnostic agreement with TCM practitioners for diagnosing TCM syndrome types in IBS after learning the diagnostic criteria. This knowledge can aid gastroenterologists in selecting suitable Chinese patent medicine to treat IBS.

The efficacy of Bifidobacterium quadruple viable tablet in the treatment of diarrhea predominant irritable bowel syndrome: protocol for a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Leading to significant negative effect on patients' quality of life and huge financial burden to health system, the management of IBS is a great challenge. Probiotics are considered as an effective therapy; however, in a lack of high-quality evidence of efficacy, no strain- and dose-specific probiotics were recommended in clinical guidelines. This study aims to evaluate the efficacy of the Bifidobacterium quadruple viable tablet in the treatment of IBS-D. METHODS/DESIGN: A multicenter randomized controlled trial will be performed in fourteen hospitals. A total of three hundred patients who fulfill the eligibility criteria will be stratified divided into an experimental group and a control group randomly in a ratio of 1:1. The experimental group is treated with the Bifidobacterium quadruple viable tablet while the control group is treated with placebo. All the patients will receive a 4-week treatment and a 2-week follow-up. The primary outcome is the effectiveness in improving abdominal pain and stool consistency; the secondary outcome includes evaluation of overall symptom relief, frequency of defecation, bloating, urgency of defecation, remedial medication, score of IBS-QOL, and changes of microbiota and metabonomics. Physical examination, vital signs, laboratory tests, adverse events, and concomitant medication will be taken into account for intervention safety assessment during the trial. DISCUSSION: This multicenter randomized controlled trial may provide high-quality evidence on the efficacy of the Bifidobacterium quadruple viable tablet for IBS-D on both physical and mental dimensions in China. To fill the gap of previous probiotic intervention studies, in addition, this study will also present safety assessment which will be a significant emphasis. TRIAL REGISTRATION: ChiCTR1800017721 . Registered on 10 August 2018.

Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice.

BACKGROUND: The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined. AIMS: To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model. METHODS: T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention. RESULTS: Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice. CONCLUSIONS: PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.

The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making. METHODS: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing. FINDINGS: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p < .05). Several metabolic pathways were more abundant in H. pylori-positive communities while some disease-associated pathways had higher potential in H. pylori-negative community through KEGG pathway analysis. Abundances of most butyrate-producing bacteria significantly decreased, while several detrimental bacteria increased after eradication therapy. Probiotic supplementation was associated with improved gastrointestinal symptoms as well as increased Bacteroidetes:Firmicutes ratio. INTERPRETATION: While H. pylori infection may not be necessarily detrimental in all patients, eradication of H. pylori was associated with widespread changes in gut microbial ecology and structure. Probiotic supplementation could relieve more gastrointestinal symptoms by inducing alterations in gut microbiota and host immune responses. As such, the decision to eradicate H. pylori should be based on comprehensive analysis of individual patients.

Altered Intestinal Microbiota with Increased Abundance of Prevotella Is Associated with High Risk of Diarrhea-Predominant Irritable Bowel Syndrome.

Alterations in gut microbiota are postulated to be an etiologic factor in the pathogenesis of irritable bowel syndrome (IBS). To determine whether IBS patients in China exhibited differences in their gut microbial composition, fecal samples were collected from diarrhea-predominant IBS (IBS-D) and healthy controls and evaluated by 16S ribosomal RNA gene sequence and quantitative real-time PCR. A mouse model of postinfectious IBS (PI-IBS) was established to determine whether the altered gut microbiota was associated with increased visceral hypersensitivity. The results indicated that there were significant differences in the bacterial community profiles between IBS-D patients and healthy controls. Prevotella was more abundant in fecal samples from IBS-D patients compared with healthy controls (p < 0.05). Meanwhile, there were significant reductions in the quantity of Bacteroides, Bifidobacteria, and Lactobacillus in IBS-D patients compared with healthy controls (p < 0.05). Animal models similarly showed an increased abundance of Prevotella in fecal samples compared with control mice (p < 0.05). Finally, after the PI-IBS mice were cohoused with control mice, both the relative abundance of Prevotella and visceral hypersensitivity of PI-IBS mice were decreased. In conclusion, the altered intestinal microbiota is associated with increased visceral hypersensitivity and enterotype enriched with Prevotella may be positively associated with high risk of IBS-D.

Efficacies of different proton pump inhibitor-based 14-day bismuth-furazolidone quadruple regimens for the initial eradication of Helicobacter pylori in the southeast coastal region of China: an open-label, randomized clinical trial.

To evaluate potency and safety of 14-day bismuth-furazolidone quadruple regimens and to compare efficacies of five proton pump inhibitors (PPIs) for the initial eradication of Helicobacter pylori (H. pylori), 175 eligible patients were enrolled and randomly assigned to 14-day quadruple regimens consisting of bismuth (400 mg), amoxicillin (1 g), furazolidone (100 mg), and a PPI, twice a day. PPIs used were Group A (pantoprazole capsules, 40 mg), Group B (pantoprazole tablets, 40 mg), Group C (lansoprazole, 30 mg), Group D (esomeprazole, 20 mg), and Group E (rabeprazole, 10 mg). H. pylori status was reassessed by 13C urea breath test on day 56 as the primary outcome. Gastrointestinal symptoms, parenteral side effects, compliance, and stool type were recorded simultaneously. The total eradication rates were 86.9% (152/175 [95% CI 80.9-91.5%]) and 95.6% (152/159 [91.1-98.2%]) by intention-to-treat (ITT) and per-protocol (PP) analysis. The efficacies of Group A, B, C, D, and E by ITT analysis were 91.4% (32/35 [76.9-98.2%]), 85.7% (30/35 [69.7-95.2%]), 88.6% (31/35 [73.3-96.8%]), 85.7% (30/35 [69.7-95.2%]), and 82.9% (29/35 [66.4-93.4%]) (p > 0.05). In the PP analysis, the efficacies were 97.0% (32/33), 93.8% (30/32), 93.9% (31/33), 100% (30/30), and 93.5% (29/31) (p > 0.05). Gastrointestinal symptoms and stool type were improved significantly (p < 0.05). Total side effects rate and poor compliance rate were 15.7% (25/159) and 5.0% (8/159). Fourteen-day bismuth-furazolidone quadruple regimens are of high potency and safety for the initial eradication of H. pylori. Efficacies of different PPIs and different dosages (9-32 mg omeprazole equivalents) showed no significant difference. The appropriate PPI can thus be chosen by clinicians.

1-Day or 5-Day Fecal Samples, Which One is More Beneficial to be Used for DNA-Based Gut Microbiota Study.

Fecal sample collection is an important influential factor for DNA-based gut microbiota study. It is controversial whether the microbiome detected in fecal sample collected at one random day could fully represent the gut microbial community. The aim of the study is to figure out whether the use of fecal sample mixture collected at consecutive 5 days could more accurately represent gut microbial community. 1- and 5-day fecal samples were collected from 8 healthy adults and analyzed by 16S rRNA sequence. Our results indicated that both 1-day fecal samples and 5-day samples exhibited relatively high repeatability. The relative abundance of majority of bacterial taxa did not changed between 1-day fecal samples and 5-day fecal samples. However, the alpha diversity of 5-day fecal samples was higher than that of 1-day fecal samples. When the aims of studies are to analyze the relative abundance of specific OTUs among subjects, fecal samples collected at one day could be used. When microbial diversity is one of essential factors to be analyzed, the use of 5-day fecal samples may be more recommended.

Small Intestinal Bacterial Overgrowth in Patients with Irritable Bowel Syndrome: Clinical Characteristics, Psychological Factors, and Peripheral Cytokines.

Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS). Psychosocial factors and low-grade colonic mucosal immune activation have been suggested to play important roles in the pathophysiology of IBS. In total, 94 patients with IBS and 13 healthy volunteers underwent a 10 g lactulose hydrogen breath test (HBT) with concurrent (99m)Tc scintigraphy. All participants also completed a face-to-face questionnaire survey, including the Hospital Anxiety and Depression Scale, Life Event Stress (LES), and general information. Serum tumour necrosis factor-α, interleukin- (IL-) 6, IL-8, and IL-10 levels were measured. The 89 enrolled patients with IBS and 13 healthy controls had no differences in baseline characteristics. The prevalence of SIBO in patients with IBS was higher than that in healthy controls (39% versus 8%, resp.; p = 0.026). Patients with IBS had higher anxiety, depression, and LES scores, but anxiety, depression, and LES scores were similar between the SIBO-positive and SIBO-negative groups. Psychological disorders were not associated with SIBO in patients with IBS. The serum IL-10 level was significantly lower in SIBO-positive than SIBO-negative patients with IBS.

Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea.

AIM: To validate 4-sample lactose hydrogen breath testing (4SLHBT) compared to standard 13-sample LHBT in the clinical setting. METHODS: Irritable bowel syndrome patients with diarrhea (IBS-D) and healthy volunteers (HVs) were enrolled and received a 10 g, 20 g, or 40 g dose lactose hydrogen breath test (LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h (13 measurements). The detection rates of lactose malabsorption (LM) and lactose intolerance (LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT. RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups (P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT (97%-100%, Kappa​​ 0.815-0.942) with high sensitivity (90%-100%) and specificity (100%) at all three lactose doses in both groups. CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.

Are there any different effects of Bifidobacterium, Lactobacillus and Streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model?

BACKGROUND AND AIMS: Research has increasingly suggested that gut flora plays an important role in the development of post-infectious irritable bowel syndrome (PI-IBS). Studies of the curative effect of probiotics for IBS have usually been positive but not always. However, the differences of treatment effects and mechanisms among probiotic stains, or mixture of them, are not clear. In this study, we compared the effects of different probiotics (Befidobacterium, Lactobacillus, Streptococcus or mixture of the three) on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model. METHODS: PI-IBS model was induced by Trichinella spiralis infection in mice. Different probiotics were administered to mice after 8 weeks infection. Visceral sensitivity was measured by scores of abdominal withdrawal reflex (AWR) and the threshold intensity of colorectal distention. Colonic smooth muscle contractile response was assessed by contraction of the longitudinal muscle strips. Plasma diamine oxidase (DAO) and d-lactate were determined by an enzymatic spectrophotometry. Expression of tight junction proteins and cytokines in ileum were measured by Western blotting. RESULTS: Compared to control mice, PI-IBS mice treated either alone with Befidobacterium or Lactobacillus (but not Streptococcus), or the mixture of the three exhibited not only decreased AWR score and contractile response, but also reduced plasma DAO and D-lactate. These probiotic treatments also suppressed the expression of proinflammatory cytokine IL-6 and IL-17 and promoted the expression of major tight junction proteins claudin-1 and occludin. The mixture of the three probiotic strains performed better than the individual in up-regulating these tight junction proteins and suppressing IL-17 expression. CONCLUSIONS: Bifidobacterium and Lactobacillus, but not Streptococcus, alleviated visceral hypersensitivity and recovered intestinal barrier function as well as inflammation in PI-IBS mouse model, which correlated with an increase of major tight junction proteins. In addition, Mixture of three species was indicated to be superior to a single one.

Characteristics of intestinal lamina propria dendritic cells in a mouse model of postinfectious irritable bowel syndrome.

BACKGROUND AND AIM: Postinfectious irritable bowel syndrome (PI-IBS), which results from inflammation has been emphasized a lot recently. Dendritic cells (DCs) may contribute to intestinal mucosal immune activation in the pathogenesis of PI-IBS. This study tested the hypothesis that phenotype and function of intestinal lamina propria DCs (LPDCs) changed in the development of a PI-IBS mouse model. METHODS: Mice infected with Trichinella spiralis underwent abdominal withdrawal reflex (AWR) to evaluate visceral sensitivity. LPDCs were isolated and purified by intestine digestion and magnetic label-based technique. Surface markers were analyzed by flow cytometry. Endocytic activity, mixed lymphocyte reaction (MLR) and chemotaxis were studied. Cytokine production of the LPDCs cocultured with CD4(+) T cells was determined. RESULTS: Intestinal inflammation resolved after 8 weeks infection with sustained visceral hyperalgesia. Surface markers CD86 and MHCII were lower in the acute infection group, but increased in the PI-IBS stage. Enhanced ability of endocytic activity and decreased abilities to attract and stimulate CD4(+) T cell proliferation were in the acute infection group. However, LPDCs in the PI-IBS stage showed weakened endocytic ability with enhanced abilities to attract and stimulate CD4(+) T cell proliferation. Cocultured LPDCs with CD4(+) T cells showed a predominant Th2 response in the acute infection stage, and more important roles of Th1, Th17 responses in the PI-IBS stage. CONCLUSIONS: The hypothesis was supported that the phenotype and function of LPDCs changed in the development of PI-IBS, which induced the maintenance of intestinal mucosal immune activation and might provide a clue for the treatment of the disease.

[Altered expression of intestinal cytokines in development of postinfectious irritable bowel syndrome mouse model].

OBJECTIVE: To observe the expression of Th1 type cytokine IL-12 and Th2 type cytokine IL-4 in different development phases of postinfectious irritable bowel syndrome in mouse model. METHODS: Mice were infected by Trichinella spiralis (350-400 Trichinella) and weighted weekly after infection. Visceral sensitivity of colorectal distention in mice was assessed by abdominal withdrawal reflex (AWR) at Weeks 0, 2, 4, 8, 12 post-infection. Tissues of terminal ileum were collected. Histological pathology and inflammation were evaluated by HE staining. RESULTS: The weights of mice in 2 and 4-week groups were lower than those in the control group [(31.1±3.7) g vs (35.6±2.7) g, (36.1±3.4) g vs (39.8±2.7) g, all P<0.05)]. The weights of 8, 12-week groups had no statistical difference with the control group (all P>0.05). Severe intestinal inflammation was observed at Week 2 during acute infectious period, but after a 4-week infection it recovered from intestinal inflammation, until Weeks 8-12, there was no difference with the control group. At 30, 45, 60 mm Hg, the AWR scores of the infectious group was higher than those in the control group. The 2-week group was the highest (2.60±0.55 vs 1.00±0.35, 2.90±0.20 vs 1.50±0.70, 3.30±0.50 vs 2.00±0.35, all P<0.05). Mice infected at Week 8 could serve as a successful model of postinfectious irritable bowel syndrome. An elevated expression of IL-12, IL-4 mRNA and protein was observed in ileocecum at Week 2 during acute phase (0.77±0.04 and 0.40±0.05, 0.42±0.04 and 0.33±0.05), decreased expression of IL-4 mRNA and protein was observed in ileocecum at Weeks 8, 12 (0.10±0.03 and 0.08±0.03, 0.08±0.03 and 0.06±0.03). However a prolonged high expression of IL-12 mRNA and protein was observed in ileocecum at Weeks 8, 12 (0.42±0.03 and 0.25±0.05, 0.39±0.02 and 0.24±0.04), but lower than those in the 2-week group (all P<0.05). CONCLUSION: A differential expression of Th type cytokines is observed in different development phases of postinfectious irritable bowel syndrome in a mouse model. All cytokines increase during acute infection stage; However Th1 type cytokine increases continuously while Th2 type cytokine decreases in the established model.

Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome.

Trimebutine maleate, which modulates the calcium and potassium channels, relieves abdominal pain in patients with irritable bowel syndrome. However, its effect on postinfectious irritable bowel syndrome is not clarified. The aim of this study was to investigate the effectiveness of trimebutine maleate on modulating colonic hypercontractility in a mouse model of postinfectious irritable bowel syndrome. Mice infected up to 8 weeks with T. spiralis underwent abdominal withdrawal reflex to colorectal distention to evaluate the visceral sensitivity at different time points. Tissues were examined for histopathology scores. Colonic longitudinal muscle strips were prepared in the organ bath under basal condition or to be stimulated by acetylcholine and potassium chloride, and consecutive concentrations of trimebutine maleate were added to the bath to record the strip responses. Significant inflammation was observed in the intestines of the mice infected 2 weeks, and it resolved in 8 weeks after infection. Visceral hyperalgesia and colonic muscle hypercontractility emerged after infection, and trimebutine maleate could effectively reduce the colonic hyperreactivity. Hypercontractility of the colonic muscle stimulated by acetylcholine and high K(+) could be inhibited by trimebutine maleate in solution with Ca(2+), but not in Ca(2+) free solution. Compared with 8-week postinfectious irritable bowel syndrome group, 2-week acute infected strips were much more sensitive to the stimulators and the drug trimebutine maleate. Trimebutine maleate was effective in reducing the colonic muscle hypercontractility of postinfectious irritable bowel syndrome mice. The findings may provide evidence for trimebutine maleate to treat postinfectious irritable bowel syndrome patients effectively.

Th17 cells influence intestinal muscle contraction during Trichinella spiralis infection.

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Th17 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-beta1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-gamma/IL-4/IL-17 cytokine production was used to analyze the proportions of CD4+ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection (PI) and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-beta1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-beta1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.

Th17 Cells Influence Intestinal Muscle Contraction during Trichinella spiralis Infection / 华中科技大学学报（医学）（英德文版）

ility might be induced by TGF-β1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.