Gastrointestinal Motility Disorders Research Articles

Defining gastrointestinal transit time using video capsule endoscopy: a study of healthy subjects.

Background and study aims Determining the etiology and location of gastrointestinal motility disorders can be challenging. A range of investigations targeting specific areas of gastrointestinal transit are available, but many provide clinical data for a given gastrointestinal region alone or for non-specific whole gut transit, and are otherwise of limited use. Video capsule endoscopy allows endoscopic visualisation of the entire gastrointestinal tract, and may also provide more specific data for regional transit time abnormalities. Patients and methods Data from video capsules ingested by 71 ambulatory healthy subjects were recorded and analyzed to determine gastric and small bowel transit times in the fasting state. Results Median, and interquartile range (IQR), gastric transit time was 22 (10–48) minutes, and median (IQR) small bowel transit time was 198.5 (157–240.5) minutes. Conclusion These data, for the first time to our knowledge, provide references for gastrointestinal transit times among healthy ambulatory subjects using video capsule endoscopy. This potentially strengthens clinical use of video capsule endoscopy in the investigation of patients with suspected gastrointestinal motility disorders.

Protein kinase A facilitates relaxation of mouse ileum via phosphorylation of neuronal nitric oxide synthase.

The enteric neurotransmitter nitric oxide (NO) regulates gastrointestinal motility by relaxing smooth muscle. Pharmacological cAMP induction also relaxes gastrointestinal smooth muscle, but it is uncertain whether cAMP augments or suppresses enteric NO signalling. In other organ systems, cAMP can increase neuronal NO production by stimulating protein kinase A (PKA) to phosphorylate neuronal NOS (nNOS) Serine-1412 (S1412). We hypothesized that cAMP also increases nNOS S1412 phosphorylation by PKA in enteric neurons to augment nitrergic relaxation of mouse ileum. We measured contractile force and nNOS S1412 phosphorylation in ileal rings suspended in an organ bath. We used forskolin to induce cAMP-dependent relaxation of wild type, nNOSS1412A knock-in and nNOSα-null ileal rings in the presence or absence of PKA, protein kinase B (Akt) and NOS inhibitors. Forskolin stimulated phosphorylation of nNOS S1412 in mouse ileum. Forskolin relaxed nNOSα-null and nNOSS1412A ileal rings less than wild-type ileal rings. PKA inhibition blocked forskolin-induced nNOS phosphorylation and attenuated relaxation of wild type but not nNOSS1412A ileum. Akt inhibition did not alter nNOS phosphorylation with forskolin but did attenuate relaxation of wild type and nNOSS1412A . NOS inhibition with L-NAME eliminated the effects of PKA and Akt inhibitors on relaxation. PKA phosphorylation of nNOS S1412 augments forskolin-induced nitrergic ileal relaxation. The relationship between cAMP/PKA and NO is therefore synergistic in enteric nitrergic neurons. Because NO regulates gut motility, selective modulation of enteric neuronal cAMP synthesis may be useful for the treatment of gastrointestinal motility disorders.

Anti-enteric neuron antibodies and gastrointestinal motility disorders

肠道神经系统对维持胃肠道功能发挥着极其重要的作用。近年来的研究显示，针对肠神经元的自身抗体可导致胃肠道运动功能的异常，可能是一些肠道动力相关疾病发生的重要机制。本文主要针对抗Hu抗体、抗钾离子通道抗体、钙离子通道抗体和抗尼古丁乙酰胆碱受体抗体等与胃肠道运动功能障碍性疾病关系的研究进展进行综述。.

Role of melatonin in intestinal mucosal injury induced by restraint stress in mice

Context A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by restraint stress, while melatonin (MT) elicits anti-inflammation and antioxidant effects. Objective The present study investigated the mechanisms of MT-mediated protection effects on restraint stress-induced GIMD. Materials and methods 144 8-week-old male ICR mice were divided into four groups: control, restraint stress, restraint stress + MT and MT (positive control). 20 mg/kg MT or vehicle were intraperitoneally injected 60 min before restraint stress (10 h/day) once daily for 3 days. Biochemical parameters, intestinal mucosal integrity, tissues antioxidant ability and autophagic proteins levels were determined. Results Mice subjected to restraint stress elevated NE level by 141.41% and decreased MT content by 38.82% in plasma. Consistent with the decrease in MT level, we observed a reduction in the antioxidant ability and an increase in autophagic proteins by 14.29–46.74% in the gut, resulting in injury to intestinal mucosa which was manifested by reductions in villus height and villus height/crypt depth (V/C) ratio, number of goblet and PCAN-positive cells, and expression of tight junction protein (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by restraint stress and improved the intestinal mucosal injury. However, there was no significant difference between MT (positive control) and control group. Discussion and conclusion Our results suggest that MT effectively mitigates psychological stress-induced injury to intestinal mucosa, providing evidence demonstrating the potential for using MT as therapy against intestinal impairment associated with psychological stress.

The inhibitory effect of somatostatin on gastric motility in Suncus murinus.

Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg−1 min−1) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10−11–10−9 M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.

Autophagy and Gastrointestinal Diseases.

Normal gastrointestinal physiology is fundamental for all the living beings. Gastrointestinal diseases mainly include gastrointestinal motility disorders, infectious inflammation (such as Helicobacter pylori infection, cholera, and intestinal parasites), non-infectious inflammation (such as chronic gastritis and Crohn's disease), and gastrointestinal cancers. In addition, intestinal microbial disorder is also an important cause of intestinal diseases, so intestinal microecological treatment (fecal microbiota transplantation) is an important mean of treating gastrointestinal diseases. In recent years, the role of autophagy in gastrointestinal diseases has been studied extensively. Autophagy is observed under various pathological processes of the gastrointestinal tract. For example, it has been demonstrated that autophagy plays an important role in maintaining the homeostasis and integrity of intestinal epithelium. Additionally, autophagy regulates host response to H. pylori infection and development of gastrointestinal cancers. Therefore, we will discuss pivotal roles of autophagy in various gastrointestinal diseases and analyze the underlying molecular mechanisms, which may provide new therapeutic targets applicable for the treatment of gastrointestinal diseases.

Nerve growth factor and Tropomyosin receptor kinase A are increased in the gastric mucosa of patients with functional dyspepsia

BackgroundNerve growth factor (NGF) and enteric glial cells (EGCs) are associated with visceral hypersensitivity and gastrointestinal motility disorder, which may represent the pathogenesis of functional dyspepsia (FD). This study aimed to investigate the expression of NGF, its high affinity receptor tropomyosin receptor kinase A (TrkA) and the EGC activation marker glial fibrillary acidic protein (GFAP) in the gastric mucosa of patients with FD and the association of these proteins with dyspeptic symptoms.MethodsGastric mucosal biopsies taken from 27 FD patients (9 epigastric pain syndrome (EPS) patients, 7 postprandial distress syndrome (PDS) patients and 11 EPS overlap PDS patients) and 26 control subjects were used for analysis. The expression of NGF, TrkA and GFAP was examined, and the association of these proteins with dyspeptic symptoms, including epigastric pain, postprandial fullness, early satiation and epigastric burning, was analysed.ResultsThe expression levels of NGF, TrkA, and GFAP in the gastric mucosa were significantly higher in the EPS group, the PDS group, and the EPS overlap PDS group than in the healthy control group. There was no significant difference between the FD subgroups. TrkA colocalized with GFAP, which indicated that TrkA was localized to EGCs, and the expression of TrkA in EGCs was significantly higher in the FD group than in the control group. Changes in the expression of NGF, TrkA, and GFAP were positively correlated with epigastric pain, postprandial fullness and early satiation but had no significant relationship with epigastric burning.ConclusionsThe increased expression of gastric NGF, TrkA and GFAP might be involved in FD pathophysiology and symptom perception.

Disorders of neural crest derivates in oncoradiological practice.

Hundreds of articles discuss the imaging characteristics and molecular background of prominent gastrointestinal (GI) motility disorders and tumors of the peripheral nervous system, but according to our knowledge an article focusing on the classification and developmental background of these heterogeneous diseases is not to be found. Our aim is to give insight on the common features of several diseases and tumors, starting with their common source of origin, the neural crest (NC). The NC is a transient cell population of the embryo, which differentiates into several organs/structures of our body (sympathetic trunk, adrenal medulla). Although the incidence of the individual tumors of NC cells is not high by themselves, the summation of these incidences may be relevant in the daily routine. In the introduction we mention the most prominent developmental routes and molecular pathways of NC cells, which is crucial to understand the pathogenesis and the wide range of involved cell types from the colon to the adrenal gland. We summarized the most important, useful pathological findings and imaging techniques from the X-ray to the positron emission tomography—computed tomography (CT) in order to help the identification of these diseases. This article may help to better understand NC lineage and its unique, diverse role during ontogeny, which may influence the radiologists to change several convictions, or understand better the background and/or connections of a wide range of tumors and syndromes.

Location, location, location: lessons from airway epithelial anion channels.

Location, location, location: lessons from airway epithelial anion channels.

Quality of metabolic control, serum potassium, and aging are the major determinants of severity of musculoskeletal disorders in hospitalized diabetic patients

Diabetes is strongly associated with numerous musculoskeletal disorders (MSD) and may be considered as another group of diabetic complications. We explored the association of diabetes type, duration, quality of metabolic control, applied therapy, and serum electrolytes, with prevalence and extent of musculoskeletal disorders as well as radiographic and EMG changes. The case-control clinical study involved 80 patients with type 1 and 2 diabetes hospitalized at General Hospital Berane and Clinical Center Podgorica, Montenegro, in 2013. More than half of the diabetics had MSD. Peripheral nerve disorders were diagnosed by EMG. The musculoskeletal disorders were evaluated using the translated Short Musculoskeletal Function Assessment (SMFA) questionnaire. The statistical methodology involved T-testing, χ2 test, Spearman’s multiple correlation, and ordinal logistic regression. The incidence and the severity of MSD were significantly related to patients age, duration of diabetes, quality of metabolic control, serum potassium, radiographic, and EMG findings. However, in the regression analysis, only aging, mean blood glucose levels, and serum potassium were associated with the significant risk for development of MSD. Advanced age, metabolic control, and hypokalemia are the main determinants of both prevalence and extent of musculoskeletal disorders in diabetics. Along with the strict glycemic control, an additional effort should be taken to avoid potassium depletion associated with diabetic ketoacidosis and to maintain optimal potassium homeostasis in diabetic patients receiving insulin, diuretics, or suffer gastrointestinal motility disorders.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats.

Background/AimsGastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated.MethodsA CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system.ResultsRats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS.ConclusionIntranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.

Functional lumen imaging probe in gastrointestinal motility diseases.

Dysfunction of gastrointestinal (GI) sphincters, including the lower esophageal sphincter (LES) at the esophagogastric junction (EGJ) and the pyloric sphincter, plays a vital role in GI motility disorders, such as achalasia, gastroesophageal reflux disease (GERD), gastroparesis, and fecal incontinence. Using multi-detector high-resolution impedance planimetry, the functional luminal imaging probe (FLIP) system measures simultaneous data on tissue distensibility and luminal geometry changes in the sphincter in a real-time manner. In this review we focus on the emerging data on FLIP, which can be used as an innovative diagnostic method during endoscopic or surgical procedures in GI motility disorders. Subsequent large, prospective, standardizing studies are needed to validate these findings before it can be put to routine clinical use.

2784 Steroid Responsive Gastric Dysmotility - Seronegative Autoimmune Autonomic Neuropathy

INTRODUCTION: Gastrointestinal motility disorders are complex conditions manifesting with a wide array of symptoms. In recent years, the increasing discovery of autoantibodies targeting the nervous system has led to the recognition of new neurologic autoimmune disorders (NAD) which present with the subacute development of profound neurological impairment and gastrointestinal motility disorders which when promptly treated with immunotherapy, may show dramatic improvement. CASE DESCRIPTION/METHODS: A 32 year old woman with a history of undifferentiated connective tissue disease presented to establish care for known gastroparesis Her symptoms started following an upper respiratory infection the age of 15 years, which was followed by development of arthralgia, rash, raynaud's, tonic pupils, and distal sensory symptoms. She also developed orthostatic intolerance and was diagnosed with severe gastroparesis with over 40 lb weight loss. Her medications included Plaquenil and methotrexate, as well as Zofran. She underwent extensive testing with autonomic function testing showing moderate sympathetic adrenergic dysfunction and distal sudomotor impairment which indicated a limited autonomic neuropathy and skin biopsy showed small fiber neuropathy. Paraneoplastic antibody testing, GAD antibody and ganglionic Acetylcholine receptor (gAChR ab) was negative. A trial of IVIg was started for suspected autoimmune GI dysmotility but this was complicated with pancytopenia. On exam she was malnourished with a BMI of 15, normal reflexes, and decreased distal sensations. She underwent repeat autonomic function testing which was normal. A 4 hour solid gastric emptying was performed which showed delayed emptying at 4 hr of 80%. She was underwent a 5 day infusion of IV Solumedrol at 1000 mg daily for suspected autoimmune dysmotility. A daily GCSI-DD ( gastroparesis cardinal symptom index- daily diary) score showed a >50% improvement in scores on Day 0 to Day 5 and normalization of 4 hour solid GES and was then started on IV Rituximab. DISCUSSION: This case highlights that importance of considering a diagnosis of neurologic autoimmune disorders which can present with as solitary GI dysmotility. Seronegative autoimmune autonomic neuropathy is a clinical entity which shows prominent sympathetic failure, sensory symptoms and is steroid responsive.

501 Prevalence of Cannabinoid Use in Patients With Gastrointestinal Symptoms

INTRODUCTION: Cannabinoids are compounds derived from the Cannabis sativa plant. These include the psychoactive delta-9-tetrahydrocannabinol (Δ9-THC), although non-psychoactive compounds such as cannabidiol also exist. Given the prevalence of cannabinoid receptors in the enteric nervous system, use of cannabinoids may contribute to the pathophysiology or treatment of gastrointestinal motility and functional disorders. However, little is known about the prevalence of cannabinoid use in patients referred to out-patient gastroenterologists. The aim of this study was to determine the prevalence of cannabinoid use, and its relation to specific gastrointestinal symptoms, in patients seen in gastroenterology clinic. METHODS: An optional survey was administered to patients attending gastroenterology clinic at a county hospital in a state where both recreational and medical cannabis use are legal. The study period was January to May of 2019. The survey queried subjects on type of cannabinoid product used, frequency of use, whether cannabinoids were used for treatment of gastrointestinal symptoms, and efficacy. Diagnosis was recorded following review of the electronic medical record. Patients who were unable to consent or those who did not demonstrate proficiency with written English were excluded. Data were analyzed with descriptive statistics using Excel (Version 16.23). Institutional Review Board approval was obtained. RESULTS: A total of 60 subjects completed the survey. Forty-nine (82%) respondents were female, and median age was 43-years-old. Twenty-nine (48%) subjects reported use of cannabinoids within the past year; the most common substances were marijuana (90%) or marijuana and cannabidiol (48%). The most common diagnosis for these subjects was chronic abdominal pain (see Figure 1). Thirty-one percent of patients reported using cannabinoids more than once daily. Twenty-eight percent of subjects reported use of cannabinoids to alleviate gastrointestinal symptoms, with a median improvement of 6 on a scale of 0-10 (0 representing no relief, 10 representing full relief). The most common reported symptom for this subset of patients was abdominal pain (see Figure 2). CONCLUSION: Use of cannabinoids, including both marijuana and cannabidiol products, was common in subjects with gastrointestinal symptoms referred to a gastroenterology clinic in a state where use is legal. More than half of subjects using cannabinoids did so for relief of a wide variety of gastrointestinal symptoms.

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment.

Inflammatory bowel diseases (IBD), Crohn`s disease and ulcerative colitis, are chronic conditions associated with high morbidity and healthcare costs. The natural history of IBD is variable and marked by alternating periods of flare and remission. Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing, a great proportion of IBD patients remain symptomatic despite effective control of inflammation. These symptoms may include but not limited to abdominal pain, dyspepsia, diarrhea, urgency, fecal incontinence, constipation or bloating. In this setting, commonly there is an overlap with gastrointestinal (GI) motility and absorptive disorders. Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment. Therefore, in this review we describe the prevalence, diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.

A Wireless Implantable System for Facilitating Gastrointestinal Motility.

Gastrointestinal (GI) electrical stimulation has been shown in several studies to be a potential treatment option for GI motility disorders. Despite the promising preliminary research progress, however, its clinical applicability and usability are still unknown and limited due to the lack of a miniaturized versatile implantable stimulator supporting the investigation of effective stimulation patterns for facilitating GI dysmotility. In this paper, we present a wireless implantable GI modulation system to fill this technology gap. The system consists of a wireless extraluminal gastrointestinal modulation device (EGMD) performing GI electrical stimulation, and a rendezvous device (RD) and a custom-made graphical user interface (GUI) outside the body to wirelessly power and configure the EGMD to provide the desired stimuli for modulating GI smooth muscle activities. The system prototype was validated in bench-top and in vivo tests. The GI modulation system demonstrated its potential for facilitating intestinal transit in the preliminary in vivo chronic study using porcine models.

Gambaran umum berbagai faktor keterlambatan pemberian nutrisi enteral pada pasien anak di Ruang Rawat Intensif Anak, RSUP Sanglah, Denpasar, Bali

Background: Enteral nutrition is the primary choice in pediatric patients who do not experience gastrointestinal disorders. Many factors inhibit the achievement of enteral nutrition in pediatric patients treated in intensive care. This study aims to determine the overview of various factors that may result in delays enteral nutrition administration in critically ill pediatric patientsMethods: An observational cross-sectional analytic study was carried out on secondary data of medical records among children who were treated in pediatric intensive care unit at Sanglah Hospital throughout 2016. Delay in enteral nutrition was assessed if there was enteral nutrition administration more than 2x24 hours since first admission. Factors assessed include gender, age, PELOD, diagnosis, invasive breathing aids, impaired motility, gastrointestinal bleeding, and hemodynamic instability. Data were analyzed using the SPSS version 20 software program whereas P value <0.05 was considered statistically significant.Results: From the 115 samples, there were 69 (60%) males and 46 (40%) females. About 50 samples (43,5%) experienced delayed enteral nutrition. Significant variables related to the delay in enteral nutrition after multivariate analysis were gastrointestinal motility disorders (p = 0,004, OR 9,082, 95% IK 2,827 – 29,171), and gastrointestinal bleeding (p = 0,0001; OR 14,317; IK 95 % 4,087 – 50,155).Conclusion Intestinal motility disorders and gastrointestinal bleeding are known as a contributing factor in the delay of enteral nutrition administration in PICU Sanglah Hospital, Denpasar, Bali.

Nutrition Management in Pediatric Gastrointestinal Motility Disorders.

Gastrointestinal (GI) motility disorders are associated with suboptimal nutrition in children, mainly because of malabsorption and symptoms limiting dietary intake. Apart from medical therapy, nutrition support has a crucial role in maintaining growth and improving clinical outcomes in children. Based on recent data and guidelines, this review provides an overview of nutrition assessment and specific interventions for common pediatric GI disorders including gastroesophageal reflux disease, esophageal motility disorders, gastroparesis, chronic intestinal pseudo-obstruction, and constipation. Several approaches including diet modification, enteral nutrition (gastric vs post-pyloric, temporary vs permanent access, bolus vs continuous), and parenteral nutrition need to be tailored based on patient's nutrition and clinical assessment.

Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders mice

ObjectiveTo compare the pharmacokinetics of naringin and neohesperidin after oral administration of Zhishi total flavonoid glycosides (ZSTFG) extracted from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders (GMD) mice. MethodsZSTFG was orally given to normal and GMD mice induced by atropine or dopamine. The plasma samples were incubated with β-glucuronidase/sulfatase, the total (free + conjugated) naringenin and hesperitin were extracted with acetonitrile. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study. ResultsThe results showed that, compared with the normal group, AUC0–∞, AUC0–t and Cmax for total naringenin and hesperitin were significantly higher (P < 0.01 or P < 0.05), while CLZ/F for total naringenin and hesperitin was significantly lower (P < 0.01) in the GMD group. Tmax, t1/2z, MRT0-t, and MRT0-∞ for naringenin were longer (P < 0.01) in the GMD group than those in the normal group. ConclusionThe results showed that there were significant differences in pharmacokinetic parameters of naringenin and hesperitin between normal and GMD groups. It was suggested that the absorption of naringenin and hesperitin was increased, and the elimination processes of naringenin and hesperitin were slower in the GMD group than the normal group. The data are of value for further pharmacological studies of ZSTFG and would be useful to provide a reference for improving the therapeutic regimen of ZSTFG in clinical trials.

An herbal-compound-based combination therapy that relieves cirrhotic ascites by affecting the L-arginine/nitric oxide pathway: A metabolomics-based systematic study

Ethnopharmacological relevanceTraditional Chinese medicine boasts a 440-year-long history of treating refractory ascites via combinations of herbal medicines, called formulae. Xiaozhang Tie (XT) is a proprietary herbal-compound-based formula that has been proven to be very effective in the treatment of cirrhosis-associated ascites in clinical practice, but the mechanism of action of XT remains unknown. Aim of the studyIn this study, we used a metabolomics-based systematic method to elucidate the mechanism of XT in the treatment of cirrhotic ascites. MethodsDecompensated liver cirrhosis was induced in rats by intraperitoneal injection of Carbon tetrachloride (CCl4). Ultra performance liquid chromatography-mass spectrometry (UPLC-MS) combined with pattern recognition approaches were used to determine differentiating metabolites relevant to XT treatment. Biomarkers were further validated by a targeted quantitative method and by the results from serum and urine analyses. Pathway analysis and correlation network construction were used to reveal the therapeutic targets associated with XT treatment, and the potential mechanisms were verified by the results from biochemical, histopathological and immunohistochemical assays. ResultsXT synergistically mediated the abnormalities of amino acid metabolic pathways in cirrhotic rats. XT significantly elevated the arginine levels, reduced the serum nitric oxide (NO) levels and alleviated the gastrointestinal motility disorder of cirrhotic rats. This effect of XT has been confirmed by the inhibition of the activities of inducible NO synthase and neuronal NO synthase in the small intestine. ConclusionsThese results reveal that XT promotes gastrointestinal motility by acting on multiple targets in multiple pathways, of which the L-arginine/NO pathway is most affected.