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.