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The pathogenesis of irritable bowel syndrome is multifactorial and complex. Our understanding of its pathophysiology has evolved, but remains incompletely understood. Symptoms result from a dysregulation of brain-gut interactions. Evidence has identified alterations in central and peripheral (gut) mechanisms in irritable bowel syndrome and the bidirectional communication between the brain and the gut. Pertinent mechanisms include disturbed gut motility, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing. This review addresses factors that increase the risk of irritable bowel syndrome and the central and peripheral mechanisms thought to underlie its symptoms.

To aid the digestion and absorption of nutrients, the gastrointestinal (GI) tract uses a carefully co-ordinated series of muscular contractions. These contractions serve to propel luminal contents through the tract, as well as churning and mixing them with enzymatic secretions to aid digestion. Smooth muscle of the GI tract exhibits fluctuations in its membrane potential that can lead to action potentials and muscle contraction. These fluctuations, known as the basal electrical rhythm, can range from around 3 to 5 per minute in the stomach to 20 per minute in the small intestine. They can be influenced by neural and hormonal input and form the basis of most muscular contractions in the GI tract. The pattern of contractions varies in different parts of the tract to serve the distinct functions of each region, for example, the stomach exhibits a reflex relaxation of muscle to accommodate a meal, while in the small intestine, segmental, mixing contractions predominate.

WOS:000629439100001 PMID: 33722110 Gastric outlet obstruction (GOO) is caused mainly by pyloric or duodenal blockage; gastric surgery and vagotomy are effective treatments. We investigated the short term effects of experimental GOO and truncal vagotomy (TV) on gut hormone levels. We used 8-week-old male Wistar rats divided randomly into four groups: control, GOO, TV, and GOO + TV. At the end of the experiment, blood and tissue samples of the pylorus and fundus were obtained for biochemical and immunohistochemical analysis. Gastric motility decreased in the TV group, but there was no difference in food intake compared to the control group; water consumption and urine output were increased. Feces excretion and food intake decreased due to loss of food movement from the stomach of GOO and GOO + TV rats. Levels of insulin and ghrelin were lower than for the control group, but levels of cholecystokinin were higher. Leptin and glucagon-like peptide 1 levels were increased in the GOO group, while somatostatin was decreased. Leptin immunostaining levels were decreased in the GOO + TV group. Gastrin and neuropeptide Y levels were lower in the GOO and GOO + TV groups compared to the other groups. We found that both gut hormone levels related to gastric motility and metabolism, and immunohistochemical staining of the stomach tissue were altered by TV and GOO. Measuring changes in gut hormones following gastric surgery could be useful for monitoring the effectiveness of treatment

Background Hirschsprung disease (HSCR) is the most common congenital gut motility disorder, involving a severe anomaly of the enteric nervous system, and is characterized by functional intestinal obstruction due to lack of intrinsic innervation (aganglionosis) in the distal bowel. Objective The aim of this study was to examine the distribution patterns of collagens I (Col I), III (Col III), and IV (Col IV) in the enteric nervous system of HSCR patients, to determine whether or not collagen levels are altered in the aganglionic bowel. Methods We measured the expression levels of Col I, Col III, and Col IV in colonic muscle from 129 children with HSCR. The localizations of the 3 collagens and myenteric ganglia were assessed morphologically by immunofluorescence staining. western blots and real-time fluorescence quantitative polymerase chain reaction were performed to examine the relative levels of these collagens in aganglionic, transitional, and ganglionic colon segments. Results Immunoreactivities of Col I and Col III were high around and within myenteric ganglia in the ganglionic segment, moderate in the transitional segment, and weak in the aganglionic segment. Col IV immunoreactivity showed the opposite pattern, being lowest in the ganglionic segment and highest in the aganglionic segment. Conclusion Col I and Col III are decreased and Col IV is increased in the distal colon of patients with HSCR.

Objective: To investigate the effect of gum chewing on recovery from post-operative ileus after elective and emergency laparotomy surgeries. Methodology: A prospective randomized study, consisting of 101 patients fulfilling the inclusion criteria was undertaken at Bangalore Baptist Hospital, Bengaluru, from January 2014 to December 2015. Commercially available chewing gum was used. The outcome of interest was time to flatus, time to bowel movement, and length of hospital stay. Results: There were significant reductions in the time to flatus and time to feces between the study group and the control group. The patients in the group got discharged a day earlier as compared to the patients in the control group {Study group (7.87 +/- 1.8 days). Control group (9.085 +/- 1.26days)}. Conclusion: In this study, the efficacy of chewing gum on post-operative ileus was well appreciated. The study group had early recovery as compared to the control group.

Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, especially bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.

Anorexia Nervosa (AN) is a complex disease that impairs the metabolic, mental and physiological health of affected individuals in a severe and sometimes lethal way. Many of the common symptoms in AN patients, such as reduced food intake, anxiety, impaired gut motility or overexercising are connected to both the orexigenic gut hormone ghrelin and the dopaminergic system. Targeting the ghrelin receptor (GhrR) to treat AN seems a promising possibility in current research. However, GhrR signaling is highly complex. First, the GhrR can activate four known intracellular pathways Gαq, Gαi/o, Gα12/13 and the recruitment of β-arrestin. Biased signaling provides the possibility to activate or inhibit only one or a subset of the intracellular pathways of a pleiotropic receptor. This allows specific targeting of physiological functions without adverse effects. Currently little is known on how biased signaling could specifically modulate GhrR effects. Second, GhrR signaling has been shown to be interconnected with the dopaminergic system, particularly in the context of AN symptoms. This review highlights that a biased agonist for the GhrR may be a promising target for the treatment of AN, however extensive and systematic translational studies are still needed and the connection to the dopaminergic system has to be taken into account.

Aims Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at three dose levels in children and determine their effects on gut motility and transit. Methods Thirty children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately one week later they were randomized to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for one week during which time the WMC test was repeated. Results Evaluable area under the plasma concentration vs. time curve (AUClast ) data were available in 29 of 30 participants. A direct linear relationship (apparent dose-proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half-life 2.1, 3.5, and 4.6 hours for the 180, 360, and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P=0.003); transit time in other regions were not affected. In contrast, stomach, small bowel, and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P Conclusions Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose-proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.

Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14–30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords “constipation”, “gastrointestinal motility”, “peristalsis”, “electrolytes”, “fluid”, “aquaporins”, and “medicine” were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.

This chapter provides a physiological basis for understanding a practical approach to patients presenting with the lower gastrointestinal symptoms. These symptoms can arise from disturbances of gut motility (diarrhoea, constipation), coordination and function of the anorectum (evacuation difficulty, faecal incontinence) and structural deficits of the hindgut (rectal bleeding). Abdominal pain is a common presentation, and can be related to physiological or anatomical changes in the gut. This chapter describes the clinical assessment of such patients to discern the likeliest diagnosis of their abdominal pain.

Background It has been proven that gut microbiota alterations are involved in the development of Henoch-Schönlein Purpura (HSP). However, the pathogenesis of HSP hasn’t been eluciated. This study was to investigate the impact of gut microbiota from HSP on ASIC3 expression and interactions between microbiota and ASIC3 expression in the development of HSP. Methods Feces collected from HSP and healthy children at the First Affiliated Hospital of Anhui Medical University were made into fecal microbial solutions. Germ-free rats were randomly assigned to either the control or HSP groups. The HSP group of rats were administered the fecal microbiota solution of HSP children, while the control group rats were administered the fecal microbiota solution of healthy children. Abdominal withdrawal reflex (AWR) and intestinal propulsion rate of the rats were used to determine visceral sensitivity. Composition of the gut microbiota of HSP children was determined using 16S rRNA gene sequencing. ASIC3 expression in the colon was ascertained through qRT-PCR as well as western blotting analysis. Results The results showed a reduction in the number of species and abundance in the intestinal microbiota of children with HSP. Visceral sensitivity and intestinal propulsion rate of HSP group rats increased significantly, compared with the control group. Colon ASIC3 mRNA and protein levels in the HSP group were found to be upregulated. The microbiota dysbiosis of HSP patients could stimulate ASIC3 expression in the colon of Germ-free rats, which in turn affected intestinal motility. Conclusions These results suggested that HSP children had intestinal microbiota disorder, which might affect gut motility by down-regulating colon ASIC3 expression in rats.

Objectives and study: Gut motility in infants mature with increasing post-menstrual age and is affected by numerous hormonal, immunological and nutritional factors. However, it remains unclear how age and diet influence gut motility and its relation to feeding intolerance and gastric residuals in preterm neonates. Using preterm piglets as a model for infants, we investigated if contrast passage rate, as determined by X-ray contrast imaging, is affected by gestational age at birth, advancing postnatal age and different milk diets.Methods: Contrast passage rate was evaluated using serial abdominal X-ray imaging on postnatal day 4 and 18 in preterm and near-term piglets fed infant formula, colostrum or intact bovine milk, with or without added fortifier (total n = 140).Results: Preterm piglets had a faster small intestinal passage rate of contrast solution at day 4 of life than near-term piglets (SIEmpty, hazard ratio (HR): 0.52, 95%CI [0.15, 0.88], p < 0.01). Formula fed piglets at day 4 had a faster passage rate of contrast to caecum (ToCecum, HR: 0.61, 95%CI [0.25,0.96], p = 0.03), and through the colon region (CaecumToRectum, p < 0.05, day 4) than colostrum fed preterm piglets. The time for contrast to leave the stomach, and passage through the colon in day 4 preterm piglets were slower than in older piglets at day 18 (both, p < 0.05). Adding a nutrient fortifier increased body growth, gastric residuals, intestinal length and weight, but did not affect any of the observed passage rates of the contrast solution.Conclusion: Serial X-ray contrast imaging is a feasible method to assess food passage rate in preterm piglets. Contrast passage rate through different gut segments is affected by gestational age at birth, postnatal age, and milk diet. The preterm piglet could be a good model to investigate clinical and dietary factors that support maturation of gut motility and thereby feeding tolerance and gut health in preterm infants.

International audience; Chronic constipation is one of the most prominent prodromal symptoms in Parkinson's disease (PD), and Lewy bodies, enriched with aggregated α-Synuclein (α-Syn), propagation from the gut into the brain has been proposed to play a key role in PD etiopathogenesis. BDNF (Brain-derived neurotrophic factor) and Netrin-1 promote both neuronal survival and regulate the gut functions. We hypothesize that C/EBPβ represses BDNF and Netrin-1 in peripheral nervous system and central nervous system, contributing to GI tract and brain malfunctions in PD. To test the hypothesis, we performed the studies in both human PD gut tissues and BDNF or Netrin-1 gut conditional KO mice models. Lewy bodies with α-Syn aggregation and neuro-inflammation were measured in the colon and brain samples from PD patients and healthy controls and rotenone or vehicle-treated WT and CEBPβ (+/-) mice. We show that both BDNF and Netrin-1 are strongly decreased in the brain and the gut of PD patients, and conditional KO of these trophic factors in the gut elicits dopaminergic neuronal loss, constipation and motor dysfunctions. Interestingly, the inflammation and oxidative stress-induced transcription factor C/EBPβ acts as a robust repressor for both BDNF and Netrin-1 and suppresses the expression of trophic factors, and its levels inversely correlate with BDNF and Netrin-1 in PD patients. Our findings support that gut inflammation induces C/EBPβ activation that leads to both BDNF and Netrin-1 reduction and triggers PD non-motor and motor symptoms. Possibly, C/EBPβ-mediated biological events might be early diagnostic biomarkers for PD.

Functional constipation (FC) is a common and often recurrent functional bowel disorder that seriously affects the quality of life of affected individuals and incurs a significant economic burden on both the individual and society. There is accumulating evidence that intestinal dysbiosis contributes to constipation and that rebalancing the gut microbiota may be a novel therapeutic modality for FC. Electroacupuncture (EA) has been shown to restore the gut microbiota to normal levels in a variety of diseases. Additionally, several high-quality clinical studies have confirmed that EA is an effective, sustained, and safe treatment for FC. However, whether the effects of EA are secondary to changes in the gut microbiota and how EA modulates intestinal dysbiosis induced by constipation are unknown. Therefore, here, we focused on the potential regulatory mechanisms of EA on diphenoxylate-induced constipation in mice by analyzing structural changes in the gut microbiota. Our results showed that EA treatment effectively rebalanced the gut microbiota of constipated mice, mainly by decreasing the Firmicutes/Bacteroidetes ratio, which may represent one way in which EA promotes gastrointestinal motility and alleviates constipation. Our findings lay the foundation for further mechanistic and clinical research into the application of EA in patients with FC.

Postoperative ileus (POI) is the transient cessation of gut motility after surgery. POI is associated with increased patient morbidity, length of hospital stay (LOS), and hospital costs. Therefore, approaches to prevent and treat POI have been research priorities, especially in the era of enhanced recovery after surgery (ERAS). The management approaches for POI can be subdivided into preventative strategies, supportive measures, and directed therapies. Some of the strategies in prevention include choice of anesthesia, surgical technique, and postoperative analgesics.

Enhanced recovery after surgery (ERAS) programs for orthopedics involve a multidisciplinary approach to accelerating return to function, reducing pain, improving patient comfort and satisfaction, reducing complications from the surgical procedure, reducing hospital length of stay, and reducing costs. ERAS pathways for patients receiving total knee arthroplasty are different from those having intracavitary surgery; they are less focused on fluid homeostasis and gut motility than they are with optimizing systemic and local analgesics and providing a balance between the highest quality pain control and accelerated return to ambulation.

Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.

Parkinson's disease is the second-most common neurodegenerative disorder worldwide. Besides deciphering the mechanisms that underlie the etiology of the disease, it is important to elucidate the factors that influence the efficacy of the treatment therapeutics. Levodopa, which remains the golden treatment of the disease, is absorbed in the proximal small intestine. A reduction in levodopa absorption, leads to reduction in striatal dopamine levels and, in turn, an “off”-episode. In fact, motor fluctuations represent a major problem during the progression of the disease and alteration between “on” (mobility often with dyskinesia) and “off” (immobility, akinesia) episodes contribute to a decreased quality of life. Dietary amino acids can interfere with the absorption of levodopa from the gut lumen and its transport through the blood brain barrier. In addition, higher abundance of specific gut bacteria that restrict levodopa absorption plays a significant role in motor fluctuations in a subset of Parkinson's disease patients. Here, we review the impact of factors potentially interfering with levodopa absorption, focusing on levodopa transport, diet, and gut bacterial interference with the bioavailability of levodopa.

The goal of the present review is to explore the relationship between dietary changes and alterations in gut microbiota that contribute to disorders of gut motility and obesity. We review the microbiota changes that are seen in obesity, diarrhea, and constipation and look at potential mechanisms of how dysbiosis can predispose to these. We find that microbial metabolites, particularly short chain fatty acids, can lead to signaling changes in the host enterocytes. Microbial alteration leading to both motility disorders and obesity may be mediated by the release of hormones including glucagon-like peptides 1 and 2 (GLP-1, GLP-2) and polypeptide YY (PYY). These pathways provide avenues for microbiota-targeted interventions that can treat both disorders of motility and obesity. In summary, multiple mechanisms contribute to the interplay between the microbial dysbiosis, obesity, and dysmotility.

Whey protein is rich in the branched-chain amino acids, L-leucine, L-isoleucine and L-valine. Thus, branched-chain amino acids may, at least in part, mediate the effects of whey to reduce energy intake and/or blood glucose. Notably, 10 g of either L-leucine or L-isoleucine, administered intragastrically before a mixed-nutrient drink, lowered postprandial blood glucose, and intraduodenal infusion of L-leucine (at a rate of 0.45 kcal/min, total: 9.9 g) lowered fasting blood glucose and reduced energy intake from a subsequent meal. Whether L-valine affects energy intake, and the gastrointestinal functions involved in the regulation of energy intake, as well as blood glucose, in humans, is currently unknown. We investigated the effects of intraduodenally administered L-valine on antropyloroduodenal pressures, plasma cholecystokinin, blood glucose and energy intake. Twelve healthy lean men (age: 29 &plusmn, 2 years, BMI: 22.5 &plusmn, 0.7 kg/m2) were studied on 3 separate occasions in randomised, double-blind order. Antropyloroduodenal pressures, plasma cholecystokinin, blood glucose, appetite perceptions and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of L-valine at 0.15 kcal/min (total: 3.3 g) or 0.45 kcal/min (total: 9.9 g), or 0.9% saline (control). Energy intake from a buffet-meal immediately after the infusions was quantified. L-valine did not affect antral, pyloric (mean number, control: 14 &plusmn, 5, L-Val-0.15: 21 &plusmn, 9, L-Val-0.45: 11 &plusmn, 4), or duodenal pressures, plasma cholecystokinin (mean concentration, pmol/L, control: 3.1 &plusmn, 0.3, L-Val-0.15: 3.2 &plusmn, L-Val-0.45: 3.0 &plusmn, 0.3), blood glucose, appetite perceptions, symptoms or energy intake (kcal, control: 1040 &plusmn, 73, L-Val-0.15: 1040 &plusmn, 81, L-Val-0.45: 1056 &plusmn, 100), at either load (p &gt, 0.05 for all). In conclusion, intraduodenal infusion of L-valine, at loads that are moderately (3.3 g) or substantially (9.9 g) above World Health Organization valine requirement recommendations, does not appear to have energy intake- or blood glucose-lowering effects.

Background: There is evidence that digestive motor disorders are frequently present in untreated celiac disease (CD) patients. Similarly, non-celiac gluten sensitivity (NCGS) can be associated with gut motor disorders. In both cases, gut dysmotility can improve or be completely reversed with a gluten-free diet (GFD). Methods: A literature search for motility disorders in CD and NCGS patients was carried out using the online databases PubMed, Medline and Cochrane. Results: Esophageal, gastric, small bowel and gallbladder motor disorders are common in both children and adults with CD. Although the clinical consequences of these disorders are not clearly defined, gastric dysfunction could affect drug absorption and metabolism in the thyroid and neurological conditions associated with CD. The impact of a GFD on motility disorders is, however, controversial. No systematic studies are available on NCGS. NCGS frequently overlaps with irritable bowel syndrome (IBS) and similar pathophysiological mechanisms may be hypothesized. Conclusions: Mucosal damage may affect gut motility in untreated CD through perturbation of hormonal and neuro-immunomodulatory regulation. A persistent low-grade mucosal inflammation could explain the cases of persistent motor disorders despite a GFD. Further studies are needed to definitely assess the role of gut motor disorders in NCGS.

Objective 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. Methods 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). Results 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 pp = 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. Conclusion 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.

Alcoholic liver disease (ALD) is implicated in gut disturbances, both functionally and structurally. It has been noticed that the gut-liver interaction is an important feature in the prevention of systemic inflammation as well as liver health. The optimal functioning of the gut-liver axis depends on gut health. Therefore, gut problems may be important for estimating liver inflammation, while our knowledge of ALD could also provide an insight into gut health. Gut problems accompanied by ALD include gut motility and absorption problems, mucosal damage and the dysbiosis of gut microbiota and gastrointestinal carcinogenesis. Moreover, there is emerging evidence that besides direct inflammatory injury caused by alcohol, gut problems related to ALD play a crucial role in the pathogenesis of cardiovascular and immunological disorders. In this regard, we should consider ALD in relation to both gut health and chronic systemic low-grade inflammation. Accordingly, integrative therapeutic strategies are warranted for treating and preventing ALD and systemic inflammation as well as alcohol-related gut problems.

Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome.

Acute gastrointestinal injury (AGI) is common in critical illness and negatively affects outcome. A variety of definitions have been used to describe AGI, which has led to clinical confusion and hampered comparison of research studies across institutions. An international working group of the European Society of Intensive Care Medicine was convened to standardize definitions for AGI and provide current evidence-based understanding of its pathophysiology and management. This disorder is associated with a wide variety of signs and symptoms and may be difficult to detect, therefore a high index of suspicion is warranted.

Pediatric functional gastrointestinal disorders (FGIDs) are disorders of the brain-gut axis. Pathophysiological factors include alterations in gut motility, microbiota, immune system, central nervous system, and psychosocial factors. Given the complex pathophysiology of FGIDs, many patients are in need of integrative treatment approaches that may include a combination of biomedical, nutritional, and psychological approaches. In this article, we examine goals of treatment; give a brief overview of biomedical, nutritional, and psychological approaches; and finally discuss the integrative management of pediatric FGIDs.

Objectives: Chronic intestinal pseudo-obstructive (CIPO) conditions are considered the most severe disorders of gut motility. They continue to present significant challenges in clinical care despite considerable recent progress in our understanding of pathophysiology, resulting in unacceptable levels of morbidity and mortality. Major contributors to the disappointing lack of progress in paediatric CIPO include a dearth of clarity and uniformity across all aspects of clinical care from definition and diagnosis to management. In order to assist medical care providers in identifying, evaluating, and managing children with CIPO, experts in this condition within the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as well as selected external experts, were charged with the task of developing a uniform document of evidence- and consensus-based recommendations. Methods: Ten clinically relevant questions addressing terminology, diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to June 2017 using a number of established electronic databases as well as repositories. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate outcome measures for the research questions. Levels of evidence and quality of evidence were assessed using the classification system of the Oxford Centre for Evidence-Based Medicine (diagnosis) and the GRADE system (treatment). Each of the recommendations were discussed, finalized, and voted upon using the nominal voting technique to obtain consensus. Results: This evidence- and consensus-based position paper provides recommendations specifically for chronic intestinal pseudo-obstruction in infants and children. It proposes these be termed paediatric intestinal pseudo-obstructive (PIPO) disorders to distinguish them from adult onset CIPO. The manuscript provides guidance on the diagnosis, evaluation, and treatment of children with PIPO in an effort to standardise the quality of clinical care and improve short- and long-term outcomes. Key recommendations include the development of specific diagnostic criteria for PIPO, red flags to alert clinicians to the diagnosis and guidance on the use of available investigative modalities. The group advocates early collaboration with expert centres where structured diagnosis and management is guided by a multi-disciplinary team, and include targeted nutritional, medical, and surgical interventions as well as transition to adult services. Conclusions: This document is intended to be used in daily practice from the time of first presentation and definitive diagnosis PIPO through to the complex management and treatment interventions such as intestinal transplantation. Significant challenges remain to be addressed through collaborative clinical and research interactions.

This laboratory practical requires first-year students to anticipate the effects of drugs active at cholinergic and adrenergic receptors on gut motility in order to design experiments during an authentic inquiry exercise. Rather than specifying a strict sequence of drug additions that aim to provide ideal demonstrations of pharmacological and physiological antagonism, I have instead designed switches into the drugs provided and set students, working in small teams, the task of identifying the switched drugs, an inquiry activity. To extend the teamwork aspect, laboratory reports were submitted by the student teams rather than individual students. Staff observed that discussions within the teams were stimulated by the inquiry-led nature of the practical. The quality of the laboratory reports submitted by teams were substantially improved over the individual reports submitted in previous years. (Students previously worked in teams, but simply followed a list of prescribed experiments and wrote individual reports.) Although, in conversation, teams of students had an improved understanding of the regulation of gut motility by the parasympathetic and sympathetic divisions of the autonomic nervous system and could readily distinguish between pharmacological and functional antagonism, no attempt was made to evaluate learning because the revision was triggered by the observed effect of a technical error and was not otherwise planned. It is likely that laboratory practicals, in general, would benefit from inclusion of inquiry.

Background In recent years, high-resolution manometry has been used in an attempt to gain a greater insight into the physiology/pathophysiology of colonic contractile activity in healthy adults and patients with colonic motility disorders. New colonic motor patterns have been identified and characterized, however, the clinical significance of these findings remains undetermined. Purpose This review will assess the current literature on colonic high-resolution manometry and determine if this procedure has advanced our understanding of colonic motility. The limitations, future directions, and the potential of this technique to assess the effects of treatment upon colonic motor patterns will also be discussed.

The goal of this review is to review the current status of prokinetics and to place it in historical context. Impaired motility and thus propulsion have long been thought to play important roles in the pathogenesis of a number of gastrointestinal disorders including gastroesophageal reflux disease (GERD), gastroparesis, chronic idiopathic pseudo-obstruction, and constipation. Historically, disordered motility was also thought to contribute to a number of functional gastrointestinal disorders such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). As we learn more of the pathophysiology of FD, IBS, GERD, constipation, and gastroparesis, the limitations of a therapeutic strategy based on the stimulation of motility (i.e., the use of a prokinetic) have become apparent and the disappointments of the past explained. The development of prokinetic drugs has also been hampered by the non-selective nature of many of the agents studied to date which resulted in some unexpected side effects. There is still an unmet need for an effective and safe prokinetic, but drug development in this area must be mindful of the challenges of the area and the need for selectivity for a given target receptor.

Introduction: Small intestinal bacterial overgrowth syndrome (SIBO) is defined as an increased number of nonpathogenic bacteria over 10 5 organisms in 1 millilitre of small intestine content. The most common predisposing factors include, among others, gut motility disorders and chronic use of proton pump inhibitors. The results of recent studies indicate the importance of SIBO in gastrointestinal diseases. Aim: To assess the prevalence of SIBO in children with abdominal pain. Material and methods: One hundred children (59 girls and 41 boys) aged from 4 to 17 years (mean age: 10.47 ±3.73 years), hospitalised due to abdominal pain, were enrolled in the study. Hydrogen breath test (HBT) with lactulose was established among all patients. Expired air was analysed using a Gastrolyzer (Bedfont). Results: The HBT result was positive in 63 (63%) children with abdominal pain; including 40 girls (67.8%) and 23 boys (56.1%). The test was positive in the group of 29 (46%) children aged under 10 years and in the group of 34 (54%) children aged over 10 years. Among the patients who reported for the control study 88% achieved a normalisation of HBT after treatment. Conclusions: The prevalence of positive HBT results in the group of patients with abdominal pain is over 60%. Small intestinal bacterial overgrowth syndrome should be considered as one of the causes of abdominal pain in children. The SIBO in children shows a good response to treatment.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to health-care services. The diagnosis of IBS is currently performed by means of symptom-based diagnostic criteria, but there has been an ongoing interest in developing biomarkers which could simplify the diagnosis and/or evaluating the effect of treatments. This article reviews the current literature concerning the proposed biomarkers including those of altered gut motility, of visceral hypersensitivity, of abnormal brain mechanisms, of serum, fecal and mucosal inflammation and of increased intestinal permeability.

The most important reason for functional diarrhea in clinical practice is diarrhea-predominant irritable bowel syndrome (IBS) which is characterized by chronic intermittent diarrhea and abdominal pain. The pathophysiology underlying IBS is complex and includes visceral hypersensitivity, abnormal gut motility and autonomous nervous system dysfunction as well as genetic and psychosocial factors. Treatment should be tailored to the individual's symptoms and involves general measures, pharmacological treatments, dietary interventions, psychotherapy and complementary and alternative approaches. The following manuscript will give an overview over pathophysiology, reasonable investigations and treatment of IBS.

Gastrointestinal manifestations are the commonest internal organ complications of systemic sclerosis and are a major cause of morbidity. The commonest features are gastro-oesophageal reflux and chronic constipation, both reflecting altered gut motility and contractility. However, there are many other manifestations that span the entire gastrointestinal tract.

Endurance horses are subjected to heightened stress even after several conditioning protocols. Hence, the goal of this study was to examine the effect of age and performance on the hematology, biochemistry, and physical parameters after an endurance race. Eighteen horses aged 6-15 years were grouped into 80-km race category. All the horses were physically examined, and blood samples were collected postrace. After physical examination, the poor (n = 9) and good (n = 9) performance horses were identified. Potassium concentration was significantly higher (P < .05) in the good performance horses; chloride concentration was significantly higher (P < .05) in the poor performance horses. The mean blood glucose concentration of the poor performance horses in all the age-groups was significantly higher (P < .05). The mean blood lactate concentration was significantly lower (P < .05) in the poor performance horses. There was significant effect of performance on heart rate (P < .031), capillary refill time (P < .013), and gut motility (P < .05). Univariate Fisher exact test results were significantly higher for skin recoil (P < .03), mucous membrane (P < .03), and gait (P < .04) in the performance categories. In conclusion, the influence of age was seen in the poor performance category in relation to lactate, but age did not influence other physical, hematological, and biochemical parameters of the endurance horses. Thus, further studies are required to determine whether physical, hematological, and biochemical parameters during training could be used to estimate performance in endurance horses based on age.

Aim Recently there has been an increased interest in using electrical stimulation to regulate gut motility generally and particularly for the treatment of slow-transit constipation. In this preliminary canine study, we aimed to study the effects of colonic electrical stimulation (CES) on colonic motility and transit. Method Nine dogs, each equipped with a pair of serosal colon electrodes and a proximal colon cannula were randomized to receive: (i) sham-CES, (ii) long pulse CES (20 cpm, 300 ms, 6 mA) or (iii) pulse train CES (40 Hz, 6 ms, 6 mA). Animals underwent assessment of colonic contractions via manometry, and of colonic transit by inserting 24 radiopaque markers via the colonic cannula and radiographically monitoring the markers at 2, 4 and 6 h following their insertion. The colonic transit was assessed by the geometric centre. Results We found that, compared with sham-CES, pulse train CES, but not long pulse CES, significantly increased the overall colonic motility index twofold and accelerated the colonic transit by 104% at 2 h, by 60% at 4 h and by 31% at 6 h (P = 0.01, P = 0.02 and P = 0.03 vs sham-CES at 2, 4 and 6 h, respectively). The accelerating effect of pulse train CES was found to be mediated via both cholinergic and nitrergic pathways. Conclusion CES with pulse trains has prokinetic effects on colonic contractions and transit in healthy dogs, mediated via the cholinergic and nitrergic pathways. Further clinical studies are warranted to explore the therapeutic potential of CES for slow colonic transit constipation.

Constipation is a particularly troublesome complaint in the elderly yet it is usually considered to be a simple management issue. Therefore physicians' lack of interest in and inadequate training about the etiology of constipation may contribute to their inability to manage the problem of constipation effectively. Constipation can become a chronic problem, refractory to management, and most likely the result of lifelong patterns of bowel and dietary habits and laxative use, along with the interaction of pathophysiological and perhaps senescent changes of gut motility. This article reviews the types and causes of constipation and the management of the problem in the elderly.

Previous patterns of energy intake influence gastrointestinal function and appetite, probably reflecting changes in small-intestinal nutrient-mediated feedback. Obese individuals consume more fat and may be less sensitive to its gastrointestinal and appetite-suppressant effects than lean individuals.To evaluate the hypothesis that, in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very-low-calorie diet (VLCD).Eight obese men (body mass index 34±0.6 kg m(-2)) were studied on two occasions, before (V1), and immediately after (V2), a 4-day VLCD. On both occasions, antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and ghrelin concentrations, and appetite perceptions were measured during a 120-min intraduodenal fat infusion (2.86 kcal min(-1)). Immediately afterwards, energy intake was quantified.During V2, basal pyloric pressure and the number and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the number of antral and duodenal PWs was less, compared with V1 (all P0.05). Moreover, during V2, baseline ghrelin concentration was higher; the stimulation of PYY and suppression of ghrelin by lipid were greater, with no difference in CCK concentration; and hunger and energy intake (kJ; V1: 4378±691, V2: 3634±700) were less (all P0.05), compared with V1.In obese males, the effects of small-intestinal lipid on gastrointestinal motility and some hormone responses and appetite are enhanced after a 4-day VLCD.

Purpose of review Motility disturbances often occur in critically ill patients resulting in an increased rate of morbidity and mortality. Only limited options for treatment of gastrointestinal dysfunction have been introduced. Factors contributing to motility disorders in the ICU patient, and recent therapeutic approaches are reviewed in the following. Recent findings Despite the growing use of early enteral nutrition in the ICU and improvements in patients' outcome, feed intolerance and motility disorders in critical illness remain unsolved. Evaluation of pathophysiological patterns such as antro-pyloric dysfunction has led to a better knowledge of gut function, whereas development of new prokinetic agents is scarce, and enthusiasm has been cut by the withdrawal of some propulsive agents from the market. Summary The complexity of gastrointestinal motor function poses a challenge to the pharmacological modulation of gut motility. There has been progress in the understanding of pathophysiologic patterns, whereas therapeutic options are still rare. Metoclopramide and erythromycin are the best evaluated and still the most promising prokinetic agents. Only a few studies in critical illness are available, and the definite value of novel propulsive agents such as motilin agonists and μ-receptor antagonists is unclear due to small patient populations. The most reasonable approach of motility disorders in critical illness seems to be an individual assessment of all associated risk factors combined with early enteral nutrition and use of prokinetic agents.

James Lubawski, Theodore SaclaridesSection of Colon and Rectal Surgery, Rush University Medical Center, Chicago, IL, USAAbstract: Postoperative Ileus (POI) is a frequent, frustrating occurrence for patients and surgeons after abdominal surgery. Despite significant research investigating how to reduce this multi-factorial phenomenon, a single strategy has not been shown to reduce POI’s significant effects on length of stay (LOS) and hospital costs. Perhaps the most significant cause of POI is the use of narcotics for analgesia. Strategies that target inflammation and pain reduction such as NSAID use, epidural analgesia, and laparoscopic techniques will reduce POI but are accompanied by a simultaneous reduction in opioid use. Pharmacologic means of stimulating gut motility have not shown a positive effect, and the routine use of nasogastric tubes only increases morbidity. Recent multi-site phase III trials with alvimopan, a peripherally acting mu-antagonist, have shown significant reductions in POI and LOS by 12 and 16 hours, respectively, by blunting the effects of narcotics on gut motility while sparing centrally mediated analgesia. Use of alvimopan, along with a multi-modal postoperative treatment plan involving early ambulation, feeding, and avoiding nasogastric tubes, will likely be the crux of POI treatment and prevention.Keywords: postoperative ileus, alvimopan, abdominal surgery

The National Institute of Child Health and Human Development and the Digestive Diseases Interagency Coordinating Committee held a workshop, chaired by Dr. W. Allan Walker, on July 10-11, 2006, to identify promising leads in necrotizing enterocolitis (NEC) research. The goals of the workshop were to identify new approaches to the prevention and treatment of NEC, to define basic and translational mechanisms of potential approaches to NEC, and to develop recommendations for clinical studies to reduce the incidence of NEC. Workshop participants implicated prematurity, introduction of enteral feedings, gastrointestinal bacterial colonization, gut motility, proinflammatory cytokines, impaired gut blood flow, and various neonatal complications in the pathogenesis of NEC. They concluded that a unifying hypothesis encompassing these pathogenetic factors is the uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants. The inflammatory cascade appears to offer multiple targets for interventions with a variety of anti-inflammatory agents, including human milk and probiotics. Because of the rapidity with which the inflammatory response gets out of control in infants with NEC, workshop participants agreed that searching for ways to prevent NEC will be more rewarding than trying to identify ways to treat the condition once it has become established.

Irritable bowel syndrome (IBS) is a common gastrointestinal condition whose cause remains unknown. Therefore, most of our effort in treating IBS has been based on a symptom approach. Recent evidence is beginning to suggest that subjects with IBS may have an alteration in gastrointestinal flora. Specifically, findings suggest that IBS patients have excessive bacteria in the small bowel, known as bacterial overgrowth. Although diagnostic testing for bacterial overgrowth is somewhat controversial, as there is no true gold standard test for bacterial overgrowth, antibiotic-based therapies for IBS are now shown to be very effective in treating IBS. Follow-up work in this area has even begun to demonstrate associative factors between gut bacteria and IBS that may explain the different types of IBS. The best example of this is the finding that methanogenic organisms in IBS patients are wholly associated with constipation-predominant IBS. It seems that the methane gas emitted during fermentation may have an influence on gut motility. In this review, the evidence for gut ecology associations in IBS is presented. A treatment algorithm also is proposed based on these findings. New areas of research in IBS such as gut bacteria are changing the treatment approach in IBS from a symptom-based style to one that is hypothesis driven.