Background-Cellular changes associated with diabetic and idiopathic gastroparesis are not well described.Aim-Describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis.Methods-Full thickness gastric body biopsies were obtained from 40 gastroparetics (20 diabetic) and matched controls. Sections were stained for H&E and trichrome, and immunolabeled with antibodies against PGP 9.5, nNOS, VIP, substance P and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68, for immune cells and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy (TEM).Results-Histological abnormalities were found in 83% of patients. Most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression which was decreased in more idiopathic gastroparetics (40%) compared to diabetic (20%) patients by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders.Conclusion-This study suggests that on full thickness biopsies, cellular abnormalities are found in the majority of patients with gastroparesis. Most common findings were loss of Kit expression suggesting loss of ICC and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offers hope that new therapeutic targets can be found.

Background & Aims Foodborne illness affects 15% of the United States population each year and is a risk factor for irritable bowel syndrome (IBS). We evaluated risk of, risk factors for, and outcomes of IBS after infectious enteritis Methods We performed a systematic review of electronic databases from 1994 through August 31, 2015 to identify cohort studies of the prevalence of IBS 3 months or more after infectious enteritis. We used random effects meta-analysis to calculate the summary point prevalence of IBS after infectious enteritis, as well as relative risk (compared to individuals without infectious enteritis) and host- and enteritis-related risk factors. Results We identified 45 studies, comprising 21,421 individuals with enteritis, followed for 3 months–10 years for development of IBS. The pooled prevalence of IBS at 12 months after infectious enteritis was 10.1% (95% CI, 7.2–14.1) and at more than 12 months after infectious enteritis was 14.5% (95% CI, 7.7–25.5). Risk of IBS was 4.2-fold higher in patients who had infectious enteritis in the past 12 months than in individuals in those who had not (95% CI, 3.1–5.7); risk of IBS was 2.3-fold higher in individuals who had infectious enteritis longer than 12 months ago than in individuals who had not (95% CI, 1.8–3.0). Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused bacterial infection, 13.8% developed IBS. Risk of IBS was significantly increased in women (odds ratio [OR], 2.2; 95% CI, 1.6–3.1) and with antibiotic exposure (OR, 1.7; 95% CI, 1.2–2.4), anxiety (OR, 2; 95% CI, 1.3–2.9), depression (OR, 1.5; 95% CI, 1.2–1.9), somatization (OR, 4.1; 95% CI, 2.7–6.0), neuroticism (OR, 3.3; 95% CI, 1.6–6.5), and clinical indicators of enteritis severity. There was a considerable level of heterogeneity among studies. Conclusion In a systematic review and meta-analysis, we found more than 10% of patients with infectious enteritis to later develop IBS; risk of IBS was 4-fold higher than in individuals who did not have infectious enteritis, although there was heterogeneity among studies analyzed. Women—particularly those with severe enteritis—are at increased risk for developing IBS, as are individuals with psychological distress and users of antibiotics during the enteritis.

Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most common aetiologies include diabetes, postsurgical and postinfectious, but in many cases it is idiopathic. Clinical presentation and natural history vary by the aetiology. There is significant morbidity and healthcare utilisation associated with gastroparesis. Mechanistic studies from diabetic animal models of delayed GE as well as human full-thickness biopsies have significantly advanced our understanding of this disorder. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system through paracrine and oxidative stress mediators is likely central to the pathogenesis of gastroparesis. Scintigraphy and 13C breath testing provide the most validated assessment of GE. The stagnant gastroparesis therapeutic landscape is likely to soon see significant changes. Relatively newer treatment strategies include antiemetics (aprepitant), prokinetics (prucalopride, relamorelin) and fundic relaxants (acotiamide, buspirone). Endoscopic pyloromyotomy appears promising over the short term, especially for symptoms of nausea and vomiting. Further controlled trials and identification of the appropriate subgroup with pyloric dysfunction and assessment of long-term outcomes are essential. This review highlights the clinical presentation, diagnosis, mechanisms and treatment advancements for gastroparesis.

Tryptamine, a tryptophan-derived monoamine similar to 5-hydroxytryptamine (5-HT), is produced by gut bacteria and is abundant in human and rodent feces. However, the physiologic effect of tryptamine in the gastrointestinal (GI) tract remains unknown. Here, we show that the biological effects of tryptamine are mediated through the 5-HT receptor (5-HTR), a G-protein-coupled receptor (GPCR) uniquely expressed in the colonic epithelium. Tryptamine increases both ionic flux across the colonic epithelium and fluid secretion in colonoids from germ-free (GF) and humanized (ex-GF colonized with human stool) mice, consistent with increased intestinal secretion. The secretory effect of tryptamine is dependent on 5-HTR activation and is blocked by 5-HTR antagonist and absent in 5-HTR mice. GF mice colonized by Bacteroides thetaiotaomicron engineered to produce tryptamine exhibit accelerated GI transit. Our study demonstrates an aspect of host physiology under control of a bacterial metabolite that can be exploited as a therapeutic modality. VIDEO ABSTRACT.

Background & Aims The existence of post-infection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report was to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based upon findings reported in the literature and clinical experience. Methods The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members. Results PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or prior to acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There is no evidence- based effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms. Conclusions Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based upon team consensus. We also propose areas for investigations.

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtypespecific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. ll

© 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .on already available consensus statements 3,4 . Consensus statements from other gastrointestinal societies or expert groups were searched for and included when appropriate, for example, if they were published more recently or if they covered relevant areas not specifically addressed in the previous documents 3,4 . Moreover, an updated literature search using PubMed and Medline was performed centrally by the corresponding author (J.K.) with additions from the co-authors. The literature search started on the date specified as the end date of the lite ature searches performed for two previously published consensus papers 3,4 (that is, 1 Jan 2008 for intraluminal measure ments of gastrointestinal motility and 1 Jan 2010 for transit tests); the search covered the period until 14 Apr 2016 and was generally limited to human studies. The literature search revealed 1,111 publications, of which 202 were selected on the basis of study quality (which did not include a formal evaluation, but the level of evidence was assessed in line with the Oxford Centre for Evidence-based Medicine (https://www.cebm.net/2009/06/oxford-centre-evidencebased-medicine-levels-evidence-march-2009/) and were made available to all authors. Low-quality studies were also considered if the topic was deemed rele vant and not covered otherwise. The literature search on gastric emptying included the following terms, revealing 624 papers: "gastric emptying", "gastro paresis", "dumping", "measurement", "test", "evalu ation" and "diagnosis". The literature search on intra luminal tests of gastric motility included the following terms, revealing 67 papers: "gastric", "antral", "antro duo denal", "antro duodenojejunal", "motility", "contraction", "intraluminal" and "mano metry". The literature search on small bowel transit included the following terms, revealing 130 papers: "orocaecal transit", "OCCT", "small bowel transit", "intestinal transit", "measurement", "test", "evaluation", "diagnosis", "sensitivity" and "specificity". The literature search on intraluminal tests of small bowel motility included the following terms, revealing 13 papers: "small bowel", "antroduodenal", "antroduodenojejunal", " intestinal", "intraluminal", "motility" and "manometry".The literature search on colonic transit included the following terms, revealing 222 papers: "colonic transit", "Hinton", "measurement", "test", "evaluation", "diagnosis", "sensitivity" and specificity. The literature search on intraluminal tests of colonic motility included the follow ing terms, revealing 55 papers: "colonic", " motility", "contraction", "intraluminal" and "manometry".Statements were distributed via e-mail, and each author had to confirm full agreement, minor concerns or disagreement in writing. Concerns or disagreement had to be explained. All statements with at least one author in disagreement or more than three authors with minor concerns were modi...

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.