Changes In Intestinal Motility Research Articles

Bioavailability of Orally Administered Drugs After Bariatric Surgery.

Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.

Differences in intestinal motility during different sleep stages based on long-term bowel sounds

Background and objectivesThis study focused on changes in intestinal motility during different sleep stages based on long-term bowel sounds.MethodsA modified higher order statistics algorithm was devised to identify the effective bowel sound segments. Next, characteristic values (CVs) were extracted from each bowel sound segment, which included 4 time-domain, 4 frequency-domain and 2 nonlinear CVs. The statistical analysis of these CVs corresponding to the different sleep stages could be used to evaluate the changes in intestinal motility during sleep.ResultsA total of 6865.81 min of data were recorded from 14 participants, including both polysomnographic data and bowel sound data which were recorded simultaneously from each participant. The average accuracy, sensitivity and specificity of the modified higher order statistics detector were 96.46 ± 2.60%, 97.24 ± 2.99% and 94.13 ± 4.37%. In addition, 217088 segments of effective bowel sound corresponding to different sleep stages were identified using the modified detector. Most of the CVs were statistically different during different sleep stages (p<0.05). Furthermore, the bowel sounds were low in frequency based on frequency-domain CVs, high in energy based on time-domain CVs and low in complexity base on nonlinear CVs during deep sleep, which was consistent with the state of the EEG signals during deep sleep.ConclusionsThe intestinal motility varies by different sleep stages based on long-term bowel sounds using the modified higher order statistics detector. The study indicates that the long-term bowel sounds can well reflect intestinal motility during sleep. This study also demonstrates that it is technically feasible to simultaneously record intestinal motility and sleep state throughout the night. This offers great potential for future studies investigating intestinal motility during sleep and related clinical applications.

Radiographic and histopathological study of gastrointestinal dysmotility in lipopolysaccharide-induced sepsis in the rat.

Sepsis is a highly incident condition in which a cascade of proinflammatory cytokines is involved. One of its most frequent consequences is ileus, which can increase mortality. Animal models such as that induced by systemic administration of lipopolysaccharide (LPS) are useful to deeply evaluate this condition. The effects of sepsis on the gastrointestinal (GI) tract have been explored but, to our knowledge, in vivo studies showing the motor and histopathological consequences of endotoxemia in an integrated way are lacking. Our aim was to study in rats the effects of sepsis on GI motility, using radiographic methods, and to assess histological damage in several organs. Male rats were intraperitoneally injected with saline or E. coli LPS at 0.1, 1, or 5 mg kg-1 . Barium sulfate was intragastrically administered, and X-rays were performed 0-24 h afterwards. Several organs were collected for organography, histopathology, and immunohistochemistry studies. All LPS doses caused gastroparesia, whereas changes in intestinal motility were dose-and time-dependent, with an initial phase of hypermotility followed by paralytic ileus. Lung, liver, stomach, ileum, and colon (but not spleen or kidneys) were damaged, and density of neutrophils and activated M2 macrophages and expression of cyclooxygenase 2 were increased in the colon 24 h after LPS 5 mg kg-1 . Using radiographic, noninvasive methods for the first time, we show that systemic LPS causes dose-, time-, and organ-dependent GI motor effects. Sepsis-induced GI dysmotility is a complex condition whose management needs to take its time-dependent changes into account.

Colonic motility adjustments in acute and chronic DSS-induced colitis

AimsInflammatory bowel disease is recurrent inflammation that affects the gastrointestinal tract causing changes in intestinal motility. The evolution of these changes is not completely understood. The aim of this study was to evaluate anatomical and functional changes in the colon during the development of acute and chronic DSS-induced ulcerative colitis (UC) in C57Bl/6 mice. Materials and methodsMice were relocated into 5 groups: control (GC) and groups exposed to DSS 3 % for 2 (DSS2d), 5 (DSS5d) and 7 DSS7d) days (acute UC) or 3 cycles (DSS3C; Chronic UC). Mice were monitored daily. After euthanasia, colonic tissue was assessed with histological, immunofluorescence and colon manometry methods. Key findingsUlcerative Colitis is a chronic disease characterized by overt inflammation of the colon. Here we investigate whether the morphological changes caused by UC in the colonic wall, in tuft cells and in enteric neurons also promote any alteration in colonic motility patterns. UC Promotes thickening in the colonic wall, fibrosis, reduction in the number of tuft cells and consequently goblet cells also, without promoting neuronal death however there is a change in the chemical code of myenteric neurons. All of these morphological changes were responsible for causing a change in colonic contractions, colonic migration motor complex, total time of gastrointestinal transit and therefore promoting dysmotility. Further studies stimulating a hyperplasia of tuft cells may be the way to try to keep the colonic epithelium healthy, reducing the damage caused by UC. SignificanceIncreasing disease pathology of DSS-induced UC induces structural and neuroanatomical changes and driven damage to cholinergic neurons causes colonic dysmotility, including increase of cholinergic myenteric neurons, followed by variations in the motility pattern of different regions of the colon that taking together characterize colonic dysmotility.

TRAUMATIC BRAIN INJURY-INDUCED INFLAMMATION AND GASTROINTESTINAL MOTILITY DYSFUNCTION.

Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. Using a mouse model of TBI, we further show how neuroinflammation after TBI is potentially linked to disruptions in gut homeostasis such as intestinal transit and inflammation. Methods: During a study of trauma patients performed from September 1, 2018, to September 1, 2019, at a single, level 1 trauma center, TBI patients aged 21 to 95 years were enrolled. Patients were categorized as TBI based on evidence of acute abnormal findings on head computed tomographic scan, which was a combination of isolated TBI and TBI with polytrauma. Blood and stool samples were collected between 24 h and 3 days after admission. Twelve plasma samples and 10 fecal samples were used for this study. Healthy control samples were obtained from a healthy control biobank. We examined systemic inflammation and bacterial changes in patients who sustained a TBI. In addition, TBI was induced in 9- to 10-week-old male mice; we assessed neuroinflammation, and intestine transit (motility) and bacterial changes 24 h after TBI. Results: When compared with healthy controls, TBI patients had increased systemic inflammation as evidenced by increased levels of IFN-γ and MCP-1 and a trend toward an increase of IL-6 and IL-8 ( P = 0.0551 and P = 0.0549), respectively. The anti-inflammatory cytokine, IL-4, was also decreased in TBI patients. Although there was a trend of an increase in copy number of Enterobacteriaceae and a decrease in copy number of Lactobacillus in both patients and mice after TBI, these trends were not found to be significantly different. However, TBI significantly increased the copy number of another potential pathogenic bacteria Bilophila wadsworthia in TBI patients compared with healthy controls. After a moderate TBI, mice had increased expression of TNF-α, IL-6 and IL-1β, CXCL1, s100a9, and Ly6G and decreased IL-10 in the brain lesion after TBI. This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.

Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota

Context Slow transit constipation (STC), the most common type of constipation, seriously affects the life of patients. Zhizhu decoction (ZZD), a traditional Chinese medicine compound, has is effective against functional constipation, but the mechanism is still unclear. Objective This research explores the mechanism of ZZD on STC from the perspective of metabolomics and gut microbiota. Materials and methods Fifty-four C57BL/6 mice were randomly divided into six groups (n = 9): control (control); STC (model); positive control (positive); low-dose (5 g/kg; L-ZZD), medium-dose (10 g/kg; M-ZZD), and high-dose (20 g/kg; H-ZZD) ZZD treatment. Following treatment of mice with ZZD for two weeks, the changes in intestinal motility, colon histology, intestinal neurotransmitters, and aryl hydrocarbon receptor (AHR) pathway determined the effects of ZZD on the pathophysiology of STC. LC-MS targeting serum metabolomics was used to analyze the regulation of ZZD on neurotransmitters, and 16S rRNA high-throughput sequencing was used to detect the regulation of the gut microbiome. Results ZZD had the highest content of naringin (6348.1 mg/L), and could significantly increase the 24 h defecations (1.10- to 1.42-fold), fecal moisture (1.14-fold) and intestinal transport rate (1.28-fold) of STC mice, increased the thickness of the mucosal and muscular tissue (1.18- to 2.16-fold) and regulated the neurotransmitters in the colon of STC mice. Moreover, ZZD significantly activated the AHR signaling pathway, and also affected the composition of gut microbiota in STC mice. Discussion and conclusions The beneficial effect and the possible mechanism of ZZD on STC could provide a theoretical basis for the broader clinical application of ZZD.

Electroacupuncture at Acupoint ST36 (Zusanli) Improves Intestinal Motility Dysfunction Via Increasing the Proportion of Cholinergic Neurons in Rat Ileal Myenteric Ganglia after Severe Acute Pancreatitis.

Using a severe acute pancreatitis (SAP) rat model, the mechanism of electroacupuncture (EA) were studied on the intestinal function of pancreatitis. The SAP models were established by injecting 30% L-ornithine at hourly intervals, and were divided into two groups (14 in each): SAP model group, which was not treated, and EA group, which received EA at ST36 at a frequency of 1-2 Hz and amplitude of 1 mA for 30 min twice a day. Fourteen rats were also included as the control group. After EA, the intestinal propulsion was measured. In the distal ileum myenteric plexus, the density of HuC/D and the proportion of cholinergic neurons were measured using immunohistochemistry. Compared to the SAP model group, the EA group demonstrated significant improvements in intestinal propulsion rates. Furthermore, after EA, the density of myenteric neurons in the ileum returned to normal levels and the proportion of cholinergic neurons was increased compared to the SAP model group. And finally, EA alleviated the damage to the pancreas. Thus, our results suggest that EA stimulation at ST36 can partly restore the enteric neuron function and improve intestinal motility dysfunction, therefore could ameliorate SAP. The enteric nervous system can participate in changes in intestinal motility by affecting cholinergic neurons.

Effects of Rikkunshi-To, a Japanese kampo medicine, on donepezil-induced gastrointestinal side effects in mice

Donepezil, an acetylcholinesterase inhibitor, is associated with gastrointestinal symptoms, such as nausea, vomiting, and anorexia, which may affect adherence to continuous therapy. Since Rikkunshi-To, a Japanese herbal medicine, activates the ghrelin signaling pathway and promotes gastrointestinal function, it is administered to prevent gastrointestinal symptoms. We herein investigated whether donepezil-induced gastrointestinal side effects in mice are ameliorated by Rikkunshi-To and if its therapeutic efficacy is mediated by ghrelin. Since pica behavior, the ingestion of kaolin, correlates with nausea and vomiting in humans, donepezil was intraperitoneally administered with or without Rikkunshi-To daily to mice, and food and kaolin intakes were monitored. The effects of donepezil on intestinal motility and a ghrelin receptor antagonist on donepezil-induced pica behavior, anorexia, and changes in intestinal motility were examined in mice treated with Rikkunshi-To. Pica behavior and anorexia were significantly induced by donepezil and significantly inhibited by Rikkunshi-To. Intestinal motility was significantly suppressed by donepezil and promoted by Rikkunshi-To. Furthermore, the therapeutic effects of Rikkunshi-To were antagonized by the ghrelin receptor antagonist. The present results support the therapeutic efficacy of Rikkunshi-To against donepezil-induced gastrointestinal side effects.

MRI-Based Characterization of Intestinal Motility in Children and Young Adults With Newly Diagnosed Ileal Crohn Disease Treated by Biologic Therapy: A Controlled Prospective Study.

BACKGROUND. Changes in intestinal motility in patients with newly diagnosed Crohn disease have historically been evaluated primarily in a subjective manner. OBJECTIVE. The purpose of this study was to assess longitudinal changes in objective intestinal motility scores in children and young adults with newly diagnosed ileal Crohn disease treated with biologic (anti-tumor necrosis factor-α) medical therapy compared with those in control participants. METHODS. This prospective study included 20 children and young adults (eight female and 12 male patients; mean age, 14.6 ± 2.1 [SD] years) with newly diagnosed ileal Crohn disease who were recruited between December 2018 and October 2021 as well as 15 control participants without any known gastrointestinal conditions (eight female and seven male patients; mean age, 18.1 ± 4.4 years). All participants underwent research MRI examinations of the small bowel, including dynamic cine 2D SSFP sequences. Patients with Crohn disease underwent additional research MRI examinations performed at both 6 weeks and 6 months after initiation of biologic therapy. Two operators independently derived terminal ileal intestinal motility scores from the dynamic cine sequences by use of FDA-approved software (with higher scores indicating greater intestinal motility). Intestinal motility scores were compared between patient and control groups by use of t tests, whereas changes in intestinal motility scores after treatment were assessed using linear mixed models. Interoperator absolute agreement was assessed using the intra-class correlation coefficient (ICC). RESULTS. Mean terminal ileal intestinal motility scores were not significantly different between patients with newly diagnosed ileal Crohn disease and control participants (for operator 1, 180.9 ± 63.3 vs 229.7 ± 115.2, respectively [p = .12]; for operator 2, 175.0 ± 62.2 vs 236.4 ± 117.4, respectively [p = .05]). Mean intestinal motility scores changed over time compared with baseline in response to biologic therapy, for operator 1 (180.9 ± 63.3 at baseline, 248.1 ± 104.9 at 6 weeks after treatment initiation, and 249.1 ± 73.2 at 6 months after treatment initiation [p = .04]) and operator 2 (175.0 ± 62.2 at baseline, 247.8 ± 112.7 at 6 weeks after treatment initiation, and 239.6 ± 72.7 at 6 months after treatment initiation [p = .03]). Absolute agreement in intestinal motility scores was excellent between operators (ICC = 0.89). CONCLUSION. MRI measurements of intestinal motility are dynamic in children and adults with newly diagnosed small-bowel Crohn disease, showing early increases in response to biologic therapy. CLINICAL IMPACT. MRI-based intestinal motility scores may aid individualized assessment of disease activity and treatment response in patients with small-bowel Crohn disease.

The Effects of Patchouli Alcohol on Diarrhea-Predominant Irritable Bowel Syndrome are Correlated with Phenotypic Plasticity in Myenteric Neurons and the Targeted Regulation of Myosin Va.

Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.

Possibilities of Correction of Functional Disorders of the Gastrointestinal Tract in Patients with Anxiety Disorders

Functional disorders of the gastrointestinal tract have recently occupied a niche of the most common diagnoses in gastroenterology, recognized by morphological and physiological abnormalities. Functional disorders of the gastrointestinal tract are a heterogeneous group of disorders, including not only symptoms characteristic of functional dyspepsia (14.6%) in combination with changes in intestinal motility but also irritable bowel syndrome (irritable bowel syndrome, 31.7%) and constipation. Thes

Intestinal microbiota and antibiotic-associated acute gastrointestinal injury in sepsis mice.

Background: To investigate the changes of intestinal microbiota and metabolites in sepsis mice with acute gastrointestinal injury before and after the use of antibiotics, and to explore the possible effects of these changes on the body.Methods: Twenty-four 6-8-w-old SPF-grade C57BL/6J male mice were selected, and the mice were randomly divided into three groups. The mice were treated by tail vein injection for 3 days. The intestinal motility of mice after administration was detected. The mice feces were collected for 16S rRNA and Untargeted metabonomics detection.Results: The use of antibiotics in sepsis mice can change the composition of intestinal microbiota and metabolites. LD3, AD3 and LAD3 samples had significant differences in bacterial species. Desulfovibrio was the species with a significant difference in LAD3. In addition, we found that the composition of those intestinal microbiota were correlated with changes in intestinal motility. The untargeted metabolomics analysis showed that the fecal metabolites of LD3 and LAD3 samples were significantly different. In addition to the basic metabolites, Benzoic acid and 4-Hydroxybenzoic acid were also found, and Desulfovibrio was associated with them.Conclusions: The use of antibiotics in sepsis mice can lead to changes in the intestinal microbiota and metabolite levels, which may be related to the severity of acute gastrointestinal injury in sepsis mice. Inhibiting Desulfovibrio in the intestine and using Benzoic acid and 4-Hydroxybenzoic acid as a marker for the production of Desulfovibrio may reduce the inflammatory degree of acute gastrointestinal injury in sepsis.

The High-Resolution Three-Dimensional Magnetic Detector System 3D-Magma Accurately Measures Gastric and Small Bowel Motility in People with Type 2 Diabetes with Neuropathy.

Gastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.

PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium.

Nuclear receptor PPARγ affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPARγ knockout mice (iePPARγKO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPARγKO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium. Gavage with the medium chain saturated FA-rich coconut oil did not result in differences between the two genotypes. Furthermore, the iePPARγKO mice did not exhibit defective lipid uptake and stomach emptying; however, their intestinal transit was more rapid than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPARγKO mice had higher body lean mass than the WT mice. We conclude that intestinal epithelium PPARγ is activated preferentially by long chain unsaturated FAs compared to medium chain saturated FAs. Furthermore, we hypothesize that the iePPARγKO phenotype originates from altered lipid metabolism and release in epithelial cells, as well as changes in intestinal motility.

Constipation in patients with myofascial pain syndrome as important aspect for clinical and nutritional treatment: A case-control study

ABSTRACT Objective To identify the occurrence of constipation in patients with myofascial pain syndrome and to correlate these disorders with the clinical and nutritional variables. Methods This report describes a case-control study performed with 98 adults of both sexs, including 49 patients and 49 individuals without pain. The intensity of the reported pain was evaluated using the Pain Visual Analog Scale, which provided a simple and efficient measurement of pain intensity consisting of a 10cm horizontal line with the ends marked “absence of pain” and “worst possible pain”. The occurrence of constipation was evaluated using the Rome III criteria. A multivariate linear regression was proposed to investigate risk factors between the frequency of bowel movements per week and independent variables this study. Results The mean ages of the patients and controls were 45.9 (7.6) years and 41.2 (12.2) years, respectively. The intensity of the reported pain showed a mean of 7.3 (1.6) points. The likelihood of exhibiting constipation was 4.5 times higher in the patients than in the controls (p=0.001). The number of stools per week was negatively correlated with the intensity of the reported pain (r=-0.613, p&lt;0.001). The use of benzodiazepines was negatively correlated with the frequency of bowel movements per week, while the use of muscle relaxants appeared to increase the frequency of defecation when combined with the use of benzodiazepines and adjusted for the intake of fiber, water and sexs (p=0.037). Conclusion Constipation was a frequent nosological entity in this patient population and the persistence of a change in intestinal motility showed a significant correlation with the pain intensity and low water intake. The reduction of the number of stools per week seems to be associated with the use of benzodiazepines.

Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice.

Gut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Perturbations of gut microbiota in early life have the potential to alter neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs the structural and functional integrity of the ENS, leading to gut dysmotility in juvenile mice. To induce gut dysbiosis, broad-spectrum antibiotics were administered by gavage to juvenile (3weeks old) male C57Bl/6 mice for 14days. Bile acid composition in the intestinal lumen was analysed by liquid chromatography-mass spectrometry. Changes in intestinal motility were evaluated by stool frequency, transit of a fluorescent-labelled marker and isometric muscle responses of ileal full-thickness preparations to receptor and non-receptor-mediated stimuli. Alterations in ENS integrity were assessed by immunohistochemistry and Western blot analysis. Antibiotic treatment altered gastrointestinal transit, luminal bile acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic and nitrergic neurotransmission associated with reduced number of nNOS neurons and different ileal distribution of the toll-like receptor TLR2. Functional defects were partly reversed by activation of TLR2 signalling. Gut dysbiosis caused complex morpho-functional neuromuscular rearrangements, characterized by structural defects of the ENS and increased tachykininergic neurotransmission. Altogether, our findings support the beneficial role of enteric microbiota for ENS homeostasis instrumental in ensuring proper gut neuromuscular function during critical stages of development.

Effects of Clostridium perfringens iota toxin in the small intestine of mice

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases.

Changes in Intestinal Motility and Gut Microbiota Composition in a Rat Stress Model

Background: Irritable bowel syndrome (IBS) causes chronic abdominal pain and abnormal bowel movements. The etiology involves complicated interactions among visceral hypersensitivity, disorders related to bowel movements, and stress. Changes in the microbiota affect the IBS pathophysiology. We investigated changes in colorectal motility, structure, and microbiota in response to stress due to maternal separation (MS) and corticotropin-releasing hormone (CRH) administration in rats. Summary: Neonatal rats were separated from their mothers for 3 h daily from postnatal day (PND) 2 to PND14. The control group included rats of the same age that were not separated. After MS, the rats were undisturbed for 5 weeks. At 8 weeks of age, 10 µg of CRH or saline was intravenously administered to MS and control groups. Two hours later, the number of fecal pellets was counted. Three hours after CRH or saline administration, the rats were sacrificed and colorectal tissue samples and cecal contents were collected to analyze the fecal microbiota. The number of fecal pellets was significantly greater in MS with the CRH group. Both stressors altered the microbiota composition. Key Messages: Among rats that received CRH, MS increased the colorectal motility. Stress due to MS altered the gut microbiota composition.

Electroacupuncture at acupoint ST 37(Shangjuxu) improves function of the enteric nervous system in a novel mouse constipation model.

BackgroundElectroacupuncture (EA) at acupoint ST 37 (Shangjuxu) has been used to alleviate gastrointestinal symptoms and improve gastrointestinal motility. However, the mechanisms by which EA affects the enteric nervous system (ENS) have scarcely been investigated. In this study, we investigated whether EA could improve ENS function.MethodsA constipation model was established by gastric instillation of ice-cold saline daily for 14 days. The constipated mice were divided into two groups: the model group, which was not treated, and the EA group, which received EA at ST 37 at a frequency of 2–15 HZ and an amplitude of 1 mA for 15 min a day for 3 days. A further six mice were included as a non-constipated control group. After EA treatment, intestinal propulsion and defecation time were measured. Additionally, in jejunum, ileum and proximal colon myenteric plexus, the expressions of PGP9.5 and nNOS were measured by immunohistochemistry.ResultsThe EA group demonstrated significant improvements in carbon propulsion rates and defecation time compared to model group (P < 0.05). In addition, after EA, the PGP9.5 and nNOS expression in jejunum, ileum and proximal colonic myenteric plexus was back to normal levels.ConclusionThis study suggests that EA stimulation at ST 37 is capable of ameliorating intestinal motility dysfunction, and can partly restore enteric neuron function. The ENS can participate in changes in intestinal motility by affecting inhibitory neurons.

Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility.

Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. Supernatants were obtained from biopsies of 18 IBS patients-nine with constipation (IBS-C) and nine with diarrhea-predominant IBS (IBS-D)-and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor-kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP- and/or cGMP-cyclase inhibitors). Exposure to IBS-C and IBS-D supernatants induced a significant reduction in basal tone and Ach-elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS-C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS-D supernatants partially restored the effects only on SMCs, whereas dilution of IBS-C supernatants significantly reverted the effects on muscle strips and Ach-elicited response on SMC. Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.