Gastrointestinal Motility Disorders Research Articles

Auricular vagal nerve stimulation enhances gastrointestinal motility and improves interstitial cells of Cajal in rats treated with loperamide.

Gastrointestinal (GI) motility disorders affect a large proportion of the population with limited treatment options. The aims of this study were to investigate the potential of a non-invasive method of auricular vagal nerve stimulation (aVNS) for treating GI dysmotility and to explore possible mechanisms involving slow waves and interstitial cells of Cajal (ICC). Normal rats were treated daily with loperamide for 1 week and then treated, while still on daily loperamide, with aVNS/Sham-aVNS for another 1week. Gastric emptying (GE), small intestine transit (SIT), and GI slow waves were measured. The plasma level of pancreatic polypeptide (PP) and noradrenaline (NE) was assessed by ELISA. ICC in the gastric antrum were detected by immunohistochemistry. (a) aVNS significantly increased the percentage of normal GI slow waves (p<0.05 for both fasting and postprandial states, vs. Sham-aVNS) and accelerated GE (p<0.05, vs. Sham-aVNS) and SIT (p<0.05, vs. Sham-aVNS) impaired by loperamide. (b) aVNS increased plasma PP (p<0.01) and decreased plasma NE (p<0.01), compared with Sham-aVNS. (c) Gastric ICC was decreased by loperamide (p<0.01) but increased after aVNS (p<0.01, vs. Sham aVNS). Loperamide induces upper GI dysmotility. aVNS accelerates upper GI transit and improving pace-making activity mediated via the ICC. Non-invasive aVNS may have a therapeutic potential for upper GI dysmotility.

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel

Endogenous cardiac pacemaker function regulates the rate and rhythm of cardiac contraction. The mutation p.Lys23Glu in the cohesin protein Shugoshin-1 causes severe heart arrhythmias due to sinoatrial node dysfunction and a debilitating gastrointestinal motility disorder, collectively termed the Chronic Atrial and Intestinal Dysrhythmia Syndrome, linking Shugoshin-1 and pacemaker activity. Hyperpolarization-activated, cyclic nucleotide-gated cation channel 4 (HCN4) is the predominant pacemaker ion-channel in the adult heart and carries the majority of the “funny” current, which strongly contributes to diastolic depolarization in pacemaker cells. Here, we study the mechanism by which Shugoshin-1 affects cardiac pacing activity with two cell models: neonatal rat ventricular myocytes and Chronic Atrial and Intestinal Dysrhythmia Syndrome patient-specific human induced pluripotent stem cell derived cardiomyocytes. We find that Shugoshin-1 interacts directly with HCN4 to promote and stabilize cardiac pacing. This interaction enhances funny-current by optimizing HCN4 cell-surface expression and function. The clinical p.Lys23Glu mutation leads to an impairment in the interaction between Shugoshin-1 and HCN4, along with depressed funny-current and dysrhythmic activity in induced pluripotent stem cell derived cardiomyocytes derived from Chronic Atrial and Intestinal Dysrhythmia Syndrome patients. Our work reveals a critical non-canonical, cohesin-independent role for Shugoshin-1 in maintaining cardiac automaticity and identifies potential therapeutic avenues for cardiac pacemaking disorders, in particular Chronic Atrial and Intestinal Dysrhythmia Syndrome.

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

In Vivo Evaluation of Fractal Microelectrodes Towards a More Targeted and Energy‐Efficient Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a moderately effective treatment option for intractable epilepsy, depression, and pain, with promising applications in the treatment of gastrointestinal motility disorders like gastroparesis. The wide-ranging potential indications of VNS suggest an opportunity for a better understanding of underlying neural circuits that can be targeted using microscale electrodes. However, microscale Platinum (Pt) electrodes often have limited charge injection capacity due to their high impedance. Recently, we experimentally demonstrated that microscale Pt electrodes with Vicsek fractal geometry can facilitate electrochemical charge transfer more efficiently with 57% higher cathodic charge storage capacity than conventional circular microelectrodes. Here we are investigating whether the fractal electrode may be more effective in eliciting small fibers in the vagus nerve with less energy consumption due to its enhanced charge injection capability. To evaluate the in vivo performance of these novel microelectrode designs and to determine whether these electrodes are capable of stimulating small, unmyelinated C fibers that supply the stomach, we designed a cuff electrode with an array with four pairs of fractal and circular microelectrode to explore the possibility of radial selective stimulation of vagus nerve. We determined the dimension of the cuff to be 760 μm in diameter to wrap around a rat's vagus nerve so that it can withstand the swelling of the nerve from chronic implantation. We patterned fractal microelectrode to have a geometrical surface area equivalent to that of a circle with 100 μm of diameter. Using a rat model, we have stimulated the right cervical vagus nerve with fractal/circular electrode and recorded the compound action potential (CAP) distal from the stimulation site with 5-7 mm of conduction distance or the dorsal trunk of the abdominal vagus (conduction distance: 70 mm). We used an autonomous neural control (ANC) system, which can stimulate and record from the nerve with randomized stimulus parameter combinations (pulse amplitude: 0-0.4 mA, pulse width: 0.02-1 ms). We adapted a cathode-first, alternating monophasic stimulation for the reliable suppression of stimulus artifact (pulse repetition frequency: 5 Hz). Results from right cervical VNS experiments in anesthetized rats showed that both the fractal and the circular electrodes can recruit small, myelinated Ad and B fibers to a similar degree (pulse amplitude: 0-0.4 mA, pulse width: 0.1 ms) (Figure 1.), but fractal electrodes produce a more uniform and consistent fiber recruitment profile (Figure 2.). We observed volleys within the slow conduction velocity range (< 3 m/s), which we suspect to be signals from the C-fibers. Our next plan is to obtain more experimental data to statistically identify the efficiency of various electrode designs in stimulating small fibers and to investigate the electrical potential profile of these electrodes in a biophysical model.

De novo gastroesophageal reflux disease esophageal surgery in bariatrics: a literature review and analysis of the current treatment options.

With the exponential increase of worldwide obesity, the number of bariatric surgery (BaS) procedures have equally risen. The surgical management of obesity has been widely established as the standard of care for sustained weight reduction, resolution, and improvement of associated comorbidities. However, BaS itself can have postoperative deleterious effects, including de novo gastroesophageal reflux disease (GERD) and upper gastrointestinal motility disorders. The modified anatomy resulting from BaS, due to either a restrictive or hypoabsorptive component, gives this disorder a multifactorial etiology. The overall management of de novo GERD should focus on three primordial approaches: Non-surgical, endoluminal, and surgical. Even in the absence of de novo GERD following primary or secondary BaS, said disorder should be closely monitored and therapy should be catered in a case-by-case approach. Consequently, treatment strategies have been developed on this principle as to adequately resolve de novo GERD. Despite the presence of multiple and suitable treatment modalities, the operating surgeon should perform them in the best interest of the patient. Short-, medium-, and long-term outcomes should be taken into consideration prior to proceed with any type of preferred management option. This article herein presents an update on the surgical management of de novo GERD following BaS and current practical innovations.

Development of a Motility Frailty Index in Patients with Gastroparesis

Introduction: Patients with symptoms (Sx) of gastrointestinal (GI) motor disorders have limitations in physical strength and mobility. We hypothesized that physical frailty correlated with severity of GI symptoms, and that a motility frailty index (MFI) could be constructed. Patients: We conducted a prospective pilot study on 40 patients, (38 F, 2 M, mean age 39.9 years) with the following diagnoses: 10 with diabetes mellitus and 30 with non-diabetic/idiopathic disorders. Upper and lower GI Sx were quantified using an FDA-compliant, traditional patient-reported outcomes (PRO) system. Methods: Patients underwent a series of physical performance measures involving standing balance (SB), usual walk speed (UW), and chair sit-and-stands (CS). A GI motility frailty index (MFI) was constructed by fitting several models with a combination of physical performance measures and correlating with PRO. Pearson’s correlation compared the constructed index with the GI Sx PRO to construct a GI MFI. Results: The studied patients collectively showed marked limitations in mobility compared with standard performance values with mean (sd) ratios of SB = 0.87 (0.20), UW = 0.45 (0.13), and CS = 0.38 (0.17). Correlations between physical mobility and GI Sx were noted for upper GI Sx (rho = 0.47, p = 0.002) but not for lower GI Sx. Conclusions: In this pilot study of patients with GI motility disorders, we found increased physical limitations on performance-based testing, which had a statistically significant positive correlation with severity of upper GI motor Sx using a standardized PRO system. A motility frailty index has been constructed that may serve as a basis for better quantifying limitations in patient mobility.

Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System.

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

Combined use of creatinine and cystatin C improves the detection of renal dysfunction in children undergoing home parenteral nutrition.

Renal dysfunction can complicate home parenteral nutrition (HPN). The aims were, in the context of pediatric HPN, to assess renal function using the measured glomerular filtration rate (mGFR), determine the most accurate formula(s) to estimate GFR, and identify possible underlying mechanisms of renal impairment. A retrospective study was performed in 2 centers. Patients receiving HPN and aged 2-16 years without medical history of nephropathy were included. GFR was measured using iohexol clearance. Estimated GFR (eGFR) was calculated using creatinine, cystatin C-based, and combined (eGFRcr+cyst ) Schwartz formulas. A total of 36 patients (18 females) were included; they received HPN for 8 (2-16) years. The primary digestive disease was short-bowel syndrome for 16 (44%) patients, gastrointestinal motility disorder for 10 (28%), or congenital diarrhea for 10 (28%). The median (range) mGFR was 99 (33-136) ml/min/1.73 m2 ; 9 (25%) patients had mildly decreased mGFR (<90 and ≥60 ml/min/1.73 m2 ), and 2 (6%) had mildly to severely decreased mGFR (<60 ml/min/1.73 m2 ). The eGFRcr+cyst formula was the most accurate and precise to estimate GFR. A significant negative correlation between mGFR and PN duration was found for patients receiving PN for 6-7/7 days (P = .008). Activation of the renin-angiotensin system was identified in 15 of 36 (42%) patients. Renal dysfunction was frequent and correlated with the duration of PN only for patients with the most severe intestinal failure. The use of eGFRcr+cyst improves its detection in these patients. Chronic dehydration may be an underlying mechanism.

The antroduodenal transition time is prolonged in adults with type 1 diabetes.

The gastroparetic syndrome encompasses antral hypomotility, gastric dysrhythmia, impaired antroduodenal coordination, pyloric dysfunction, and abnormal duodenal motility; the last three collectively referred to as pylorospasms. We hypothesized that antroduodenal motility is diminished and transition time is prolonged in adults with type 1 diabetes (T1D) and polyneuropathy. This cross-sectional study included 124 participants, of which 21 were healthy, 53 had T1D and 50 had T1D with distal symmetrical polyneuropathy (T1D + DSPN). We used the wireless motility capsule to assess antroduodenal transition time, gastric emptying time, gastric and small bowel motility indices (MI), and numbers of alkalic/acidic exposures. In comparison with controls, patients with T1D had prolonged antroduodenal transition time (1.85±1.5 vs. 6.6±4.8 minutes; p=0.02), which was even more pronounced in patients with T1D+DSPN (1.85±1.5 vs. 17.8±28.5 minutes; p<0.008. T1D+DSPN tended to have diminished gastric MI (11.9±2.4 vs. 12.7±1.0, p=0.07) and small bowel MI (13.1±1.4 vs. 13.6±0.6, p=0.05) and experienced more antral/pyloric alkalic episodes (1.2±1.3 vs. 2.0±2.1, p=0.02) compared with controls. The current method may assess a proxy for severity of pylorospasms in patients with diabetes and other diseases associated with upper gastrointestinal motility disorders, which ultimately may optimize future management.

MiR-222 regulates cell growth, apoptosis, and autophagy of interstitial cells of Cajal isolated from slow transit constipation rats by targeting c-kit

Excessive autophagy and apoptosis of the interstitial cells of Cajal (ICC) have been identified in gastrointestinal (GI) motility disorders including slow transit constipation (STC). MicroRNA 222 (miR-222) has been shown to affect GI motility. This study aimed to explore whether miR-222 influences apoptosis and excessive autophagy of isolated ICC. miR-222, c-kit, and stem cell factor (SCF) were evaluated in colon tissues in STC rats compared with normal control by qRT-PCR and western blot analysis. The condition of autophagy of colon tissue was observed by transmission electron microscope. ICC were isolated from the colon of STC rats. Cell Counting Kit-8 (CCK-8) assay and wound healing assay were carried out to examine the cell viability and migration rate. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Annexin V-Flourescein Isothiocyanate/Propidine Iodide (FITC/PI) apoptosis detection kit. Western blot analysis was performed to detect the c-kit and SCF expression; apoptosis-related proteins Bcl-2, Bax, caspase-3, and pro-caspase-3; and autophagy-related proteins LC3B and Beclin-1. The connection between miR-222 and c-kit was detected by bioinformatics and luciferase activity analysis. miR-222 expression was significantly higher, whereas c-kit and SCF expressions were markedly lower in STC rats’ colon tissue compared with normal control. Meanwhile, STC rats exhibited excessive autophagy in colon tissue than normal control. Inhibition of miR-222 expression promoted cell proliferation as well as migration and inhibited autophagy, whereas upregulation of miR-222 had the opposite effect. In addition, miR-222 upregulation induced apoptosis and excessive autophagy compared with normal controls (NC). Western blot analysis showed that miR-222 overexpression caused decreased c-kit and SCF protein levels compared with NC. Bioinformatics and luciferase activity analysis revealed that miR-222 could be a predictive regulator of c-kit. miR-222 induces apoptosis and excessive autophagy of ICC and may serve as potential biomarker for ICC loss in STC.

Differentiated PDGFRα-Positive Cells: A Novel In-Vitro Model for Functional Studies of Neuronal Nitric Oxide Synthase

It is evident that depletion of interstitial cells and dysfunction of nitric oxide (NO) pathways are key players in development of several gastrointestinal (GI) motility disorders such as diabetic gastroparesis (DGP). One of the main limitations of DGP research is the lack of isolation methods that are specific to interstitial cells, and therefore conducting functional studies is not feasible. The present study aims (i) to differentiate telomerase transformed mesenchymal stromal cells (iMSCs) into platelet-derived growth factor receptor-α-positive cells (PDGFRα-positive cells) using connective tissue growth factor (CTGF) and L-ascorbic acids; (ii) to investigate the effects of NO donor and inhibitor on the survival rate of differentiated PDGFRα-positive cells; and (iii) to evaluate the impact of increased glucose concentrations, mimicking diabetic hyperglycemia, on the gene expression of neuronal nitric oxide synthase (nNOS). A fibroblastic differentiation-induction medium supplemented with connective tissue growth factor was used to differentiate iMSCs into PDGFRα-positive cells. The medium was changed every day for 21 days to maintain the biological activity of the growth factors. Gene and protein expression, scanning electron and confocal microscopy, and flow cytometry analysis of several markers were conducted to confirm the differentiation process. Methyl tetrazolium cell viability, nitrite measurement assays, and immunostaining were used to investigate the effects of NO on PDGFRα-positive cells. The present study, for the first time, demonstrated the differentiation of iMSCs into PDGFRα-positive cells. The outcomes of the functional studies showed that SNAP (NO donor) increased the survival rate of differentiated PDGFRα-positive cells whereas LNNA (NO inhibitor) attenuated these effects. Further experimentations revealed that hyperglycemia produced a significant increase in expression of nNOS in PDGFRα-positive cells. Differentiation of iMSCs into PDGFRα-positive cells is a novel model to conduct functional studies and to investigate the involvement of NO pathways. This will help in identifying new therapeutic targets for treatment of DGP.

Mechanotransduction in gastrointestinal smooth muscle cells: role of mechanosensitive ion channels.

Mechanosensation, the ability to properly sense mechanical stimuli and transduce them into physiologic responses, is an essential determinant of gastrointestinal (GI) function. Abnormalities in this process result in highly prevalent GI functional and motility disorders. In the GI tract, several cell types sense mechanical forces and transduce them into electrical signals, which elicit specific cellular responses. Some mechanosensitive cells like sensory neurons act as specialized mechanosensitive cells that detect forces and transduce signals into tissue-level physiological reactions. Nonspecialized mechanosensitive cells like smooth muscle cells (SMCs) adjust their function in response to forces. Mechanosensitive cells use various mechanoreceptors and mechanotransducers. Mechanoreceptors detect and convert force into electrical and biochemical signals, and mechanotransducers amplify and direct mechanoreceptor responses. Mechanoreceptors and mechanotransducers include ion channels, specialized cytoskeletal proteins, cell junction molecules, and G protein-coupled receptors. SMCs are particularly important due to their role as final effectors for motor function. Myogenic reflex-the ability of smooth muscle to contract in response to stretch rapidly-is a critical smooth muscle function. Such rapid mechanotransduction responses rely on mechano-gated and mechanosensitive ion channels, which alter their ion pores' opening in response to force, allowing fast electrical and Ca2+ responses. Although GI SMCs express a variety of such ion channels, their identities remain unknown. Recent advancements in electrophysiological, genetic, in vivo imaging, and multi-omic technologies broaden our understanding of how SMC mechano-gated and mechanosensitive ion channels regulate GI functions. This review discusses GI SMC mechanosensitivity's current developments with a particular emphasis on mechano-gated and mechanosensitive ion channels.

Gastrointestinal motility disorders in neurologic disease.

The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.

Cannabinoids in disorders of gut-brain interaction and gastrointestinal motility

Cannabinoids in disorders of gut-brain interaction and gastrointestinal motility

An easy and low-cost biomagnetic methodology to study regional gastrointestinal transit in rats.

The identification of gastrointestinal (GI) motility disorders requires the evaluation of regional GI transit, and the development of alternative methodologies in animals has a significant impact on translational approaches. Therefore, the purpose of this study was to validate an easy and low-cost methodology (alternate current biosusceptometry- ACB) for the assessment of regional GI transit in rats through images. Rats were fed a test meal containing magnetic tracer and phenol red, and GI segments (stomach, proximal, medial and distal small intestine, and cecum) were collected to assess tracer's retention at distinct times after ingestion (0, 60, 120, 240, and 360min). Images were obtained by scanning the segments, and phenol red concentration was determined by the sample's absorbance. The temporal retention profile, geometric center, gastric emptying, and cecum arrival were evaluated. The correlation coefficient between methods was 0.802, and the temporal retention of each segment was successfully assessed. GI parameters yielded comparable results between methods, and ACB images presented advantages as the possibility to visualize intrasegmental tracer distribution and the automated scan of the segments. The imaging approach provided a reliable assessment of several parameters simultaneously and may serve as an accurate and sensitive approach for regional GI research in rats.

LC-MS-based plasma metabolomics study of the intervention effect of different polar parts of hawthorn on gastrointestinal motility disorder rats.

Dyspepsia, one of the most prevalent diseases of the digestive tract that impacts the quality of patient life, is mainly caused by gastrointestinal motility disorder. Hawthorn is a commonly used traditional Chinese medicine for treating dyspepsia, and has been proven to improve gastrointestinal motility. Herein, a rat model of gastrointestinal motility disorder was established by subcutaneous injection with atropine. The modeled rats were treated with four polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn. Through metabolomics analysis, a total of 20 significantly metabolites were identified with significant changes in their abundance levels and these metabolites were related to many metabolic pathways such as amino acid metabolism and primary bile acid biosynthesis. The results showed that T3 had the best therapeutic effect of promoting gastrointestinal motility. Other parts showed no obvious therapeutic effect, demonstrating that the effective components of hawthorn may be compounds of medium polarity. T3 might achieve good therapeutic effects owing to the gastrointestinal motility promotion activity, and by rectifying the disturbed metabolic pathways in the gastrointestinal motility disorder model.

Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders.

Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.

Fecal elastase levels in children diagnosed with functional abdominal pain-not otherwise specified.

Although the exact pathophysiology of functional gastrointestinal diseases remains unclear, numerous etiologies have been blamed, including visceral hypersensitivity, gastrointestinal motility disorders, psychological factors, intestinal mucosal inflammation, intestinal microbiota, and post-infectious syndromes. In the present study, we aimed to evaluate pancreatic insufficient patients diagnosed with functional abdominal pain-not otherwise specified (FAP-NOS) according to Rome IV criteria. The study included a total of 110 patients aged 4-17 years who were diagnosed with FAP-NOS according to Rome IV criteria. The control group consisted of 80 patients with no gastrointestinal disorders and chronic diseases. Glucose, amylase, lipase, pancreatic amylase, immunoreactive trypsinogen (IRT) and fecal elastase (FE-1) levels were examined for each patient. No significant difference was found between the two groups with regard to lipase, pancreatic amylase, IRT, and serum glucose levels. However, the amylase levels were significantly higher and the FE-1 levels were significantly lower in the study group compared to the control group (p=0.007 and p < 0.001). The cut-off value detected in in ROC analysis for the diagnostic value of FE-1 in predicting FAP-NOS was found to be 140.107 μg/g. Based on this value, the sensitivity, specificity, PPV, and NPV of FE-1 were 82.1%, 66.2%, 77%, 73%, respectively. Accordingly, the likelihood of FE-1 in providing a positive value in patients with FAP-NOS was almost 9 times higher than in individuals without FAP-NOS. FE-1 levels were significantly lower in children diagnosed with FAP-NOS and we consider that this difference could be attributed to malabsorption secondary to dysbiosis as there is not enough data.

Gastrointestinal motility modulation by stress is associated with reduced smooth muscle contraction through specific transient receptor potential channel.

Excessive stress response causes disability in social life. There are many diseases caused by stress, such as gastrointestinal motility disorders, depression, eating disorders, and cardiovascular diseases. Transient receptor potential (TRP) channels underlie non-selective cation currents and are downstream effectors of G protein-coupled receptors. Ca2+ influx is important for smooth muscle contraction, which is responsible for gastrointestinal motility. Little is known about the possible involvement of TRP channels in the gastrointestinal motility disorders due to stress. The purpose of this study was to measure the changes in gastrointestinal motility caused by stress and to elucidate the mechanism of these changes. The stress model used the water immersion restraint stress. Gastrointestinal motility, especially the ileum, was recorded responses to electric field stimulation (EFS) by isometric transducer. EFS-induced contraction was significantly reduced in the ileum of stressed mouse. Even under the conditions treated with atropine, EFS-induced contraction was significantly reduced in the ileum of stressed mouse. In addition, carbachol-induced, neurokinin A-induced, and substance P-induced contractions were all significantly reduced in the ileum of stressed mouse. Furthermore, the expression of TRPC3 was decreased in the ileum of stressed mouse. These results suggest that the gastrointestinal motility disorders due to stress is associated with specific non-selective cation channel.