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Disordered motility is one of the most important pathogenic characteristics of unctional dyspepsia (FD), although the underlying mechanisms remain unclear. Since the sympathetic system is important to the regulation of gastrointestinal motility, the present study aimed to investigate the role of norepinephrine (NE) and adrenoceptors in disordered gastric motility in a rat model with FD. The effect of exogenous NE on gastric motility in control and FD rats was measured through an organ bath study. The expression and distribution of β-adrenoceptors were examined by real-time PCR, Western blotting and immunofluorescence. The results showed that endogenous gastric NE was elevated in FD rats, and hyperreactivity of gastric smooth muscle to NE and delayed gastric emptying were observed in the rat model of FD. The mRNA levels of β1-adrenoceptor and norepinephrine transporter (NET) and the protein levels of β2-adrenoceptor and NET were increased significantly in the gastric corpus of FD rats. All three subtypes of β-adrenoceptors were abundantly distributed in the gastric corpus of rats. In conclusion, the enhanced NE and β-adrenoceptors and NETs may be contributed to the disordered gastric motility in FD rats.

Effects of ethyl acetate extract of (EES) on brain-gut peptides and interstitial cells of gastric Cajal in rats with diabetic gastroparesis were explored. Rats were divided into six groups: normal control group (NC), diabetic gastroparesis model group (DGP), low, medium, and high dose of EES groups (LES, MES, and HES, respectively), and metoclopramide positive group (MPG). DGP rats were induced by streptozotocin (STZ) combined with a high-sugar-high-fat diet. The gastric emptying was measured by the phenol red labeling method. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the concentrations of serum ghrelin, gastrin (GAS), somatostatin (SS), and vasoactive intestinal peptide (VIP). The expressions of c-Kit and its natural ligand stem cell factor (SCF) in gastric tissues were determined by Western blot and immunofluorescence. Gastric emptying rate increased in a different degree after intervention by EES, among which MES and HES groups showed a significant effect (compared with DGP, <0.01) and the HES group was equivalent to the MPG group; serum ghrelin and content of serum GAS increased while SS and VIP decreased (compared with the DGP group, <0.05 or <0.01); c-Kit and SCF protein expressions in gastric tissue increased (compared with DGP group, <0.05 or <0.01). EES significantly improved gastric emptying by regulating gastrointestinal hormone excretion and c-Kit/SCF signaling pathway. Our study provides a pharmacological basis for the use of the EES in the treatment of DGP. However, the detailed molecular mechanism remains to be clarified.

Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.

Background: The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI). Patients and methods: Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with functional pylorospasm/peptic pyloric stenosis underwent real time MRI. All patients were examined on two separate days; once prior to therapy and once after adequate therapy. Antral motility was quantified by calculating the gastric motility index. Results: Patients with gastroparesis showed a lower motility index compared with the reference volunteer group while the mean motility index of the patient group with pylorospasm was more than three times higher than that of the reference value of the volunteer group. However, the gastric motility index in the patient group with gastroparesis increased, and in the group with functional pylorospasm/peptic pyloric stenosis it decreased significantly after therapy. Conclusion: Real time MRI is a reliable tool for assessment of gastric motion. Furthermore, differences in gastric motility index in patients with increased or decreased gastric motility could be evaluated and quantified. Due to the non-invasive character of MRI, this imaging modality may be an attractive alternative to conventional invasive diagnostic tools for gastric motility disorders and therapeutic monitoring.

Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.

ObjectiveHigh-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility.DesignFaecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin.ResultsTransplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice.ConclusionWe revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes.Trial registration number NCT03634644.

Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut–brain interaction (via the gut–brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut–brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.

BackgroundGastric emptying testing (GET), while useful for evaluating gastric motility, is not specific nor sensitive for neuromuscular disorders. However, Gastric Alimetry® (GA) is a novel medical test that uses gastric mapping and validated symptom profiling. The current study compared the patient-specific phenotyping from GA with GET.MethodsPatients with chronic gastroduodenal symptoms completed GET and GA concurrently. Tests included a 30-minute baseline, 99mTC-labelled egg meal and 4-hour postprandial recording. Results were compared to the reference normative ranges. The validated GA App profiled symptoms and subsequently phenotyped them using rule-based criteria into either: 1) Continuous (no correlation between symptoms and meal or gastric activity); 2) Gastric Sensorimotor (correlation between symptoms and meal or gastric activity); 3) or Other, to compare with questionnaires.Results75 patients with chronic gastroduodenal symptoms were assessed; 77% female, median age 43, median BMI 24.0. Motility abnormality detection rates were 22.7% (GET); 33.3% (GA) with a combined yield 42.7%. All groups showed similar symptom profiles and did not correlate with Rome criteria or health psychology factors (p>0.05). GA symptom phenotypes (figure 1A) were: gastric sensorimotor 17%; continuous 30%; other 53%. Strong correlations between the sensorimotor phenotype and gastric amplitude were observed (median r=0.61 vs r=0.08 and r=0.06 respectively; p=0.0002). The continuous phenotype correlated with depression and anxiety (p<0.05), while Rome IV Criteria did not (p>0.05). No correlation between GET abnormalities and GA phenotypes was found (figure 1B).ConclusionIn patients with chronic gastroduodenal symptoms, GA produced a high yield for motility abnormalities, compared to GET. Additionally, GA found correlations between patient-specific symptom phenotypes and health psychology factors, which were not identified by ROME IV and GET. Together, the results suggest that GA and GET may work in conjunction with each other by assessing different features of gastric functioning.Abstract P268 Figure 1Diagnostic evaluation by GET and GA. A) Overall diagnostic outcomes of GA spectral and symptom phenotyping. B) Sankey plot showing limited concordance between GA spectral or symptom phenotypes with GET abnormalities[Figure omitted. See PDF]

We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation. PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS). Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects. This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.