Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Prospective multicenter study to evaluate capsule endoscopy competency using a validated assessment tool.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is an established, noninvasive modality for examining the small bowel. Minimum training requirements are based primarily on guidelines and expert opinion. A validated tool to assess the competence of CE is lacking. In this prospective, multicenter study, we determined the minimum number of CE procedures required to achieve competence during gastroenterology fellowship; validated a capsule competency test (CapCT); and evaluated any correlation between CE competence and endoscopy experience. METHODS: We included second- and third-year gastroenterology fellows from 3 institutions between 2013 and 2018 in a structured CE training program with supervised CE interpretation. Fellows completed the CapCT with a maximal score of 100. For comparison, expert faculty completed the same CapCT. Trainee competence was defined as a score ≥90% compared with the mean expert score. Fellows were tested after 15, 25, and 35 supervised CE interpretations. CapCT was validated using expert consensus and item analysis. Data were collected on the number of previous endoscopies. RESULTS: A total of 68 trainees completed 102 CapCTs. Fourteen CE experts completed the CapCT with a mean score of 94. Mean scores for fellows after 15, 25, and 35 cases were 83, 86, and 87, respectively. Fellows with at least 25 interpretations achieved a mean score ≥84 in all 3 institutions. CapCT item analysis showed high interobserver agreement among expert faculty (k = 0.85). There was no correlation between the scores and the number of endoscopies performed. CONCLUSION: After a structured CE training program, gastroenterology fellows should complete a minimum of 25 supervised CE interpretations before assessing competence using the validated CapCT, regardless of endoscopy experience.

De Novo Colitis Associated With Rituximab in 21 Patients at a Tertiary Center.

Rituximab, a monoclonal antibody directed against the CD20 antigen on B lymphocytes, is commonly used in the treatment of hematologic malignancies and rheumatologic disorders.1,2 It acts to rapidly deplete the B lymphocyte population through multiple mechanisms, leading to dysregulation of the immune system.3 Rituximab has been associated with numerous adverse gastrointestinal effects including diarrhea and bowel perforation, and recent reports have associated rituximab with the development of de novo inflammatory bowel disease (IBD).4,5 To our knowledge, there have been no reports of microscopic colitis (MC) associated with rituximab therapy. We aimed to identify patients with rituximab-associated colitis, and to better characterize the clinical features and disease course of these patients.

Patient-oriented education and visual-aid intervention are inadequate to identify patients with potential capsule retention: a prospective randomized study.

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims were to determine the frequency of capsule passage visualization and the difference in self-reporting of capsule passage between patients who receive patient-oriented education (POE) and patients who receive POE and a visual aid intervention in the form of a wrist band (WB). Methods: This was a prospective randomized study that enrolled patients undergoing VCE. Patients were randomly assigned to a POE group versus a POE and WB group. POE consisted of verbal education and an information booklet. Both groups received instructions to notify the study team regarding capsule passage. Results: Sixty patients (mean age 57 ± 18 years; 61% female) were included. A total of 57 patients were included in the analysis (3 lost to follow-up; 28 in POE group; 29 in WB group). Capsule passage status was reported by 68% without significant difference between POE and WB groups (72% vs. 64%; p = .51). Capsule passage status was obtained from all 57 patients with the addition of a proactive follow-up. Only 56% (n = 32) reported visualizing capsule passage. Of the remaining patients who did not visualize capsule passage, 60% (n = 15) reported on this without significant difference between the POE and WB groups (p = .23). Conclusions: Lack of visualization of capsule passage is a poor indicator of retention. Self-reporting of VCE passage status is suboptimal and the addition of a visual aid did not improve this parameter.

Gut Microbial Carbohydrate Metabolism Hinders Weight Loss in Overweight Adults Undergoing Lifestyle Intervention With a Volumetric Diet.

The rising incidence of obesity requires the reevaluation of our current therapeutic strategies to optimize patient outcomes. The objective of this study was to determine whether compositional and functional characteristics of the gut microbiota in adults predict responses to a comprehensive lifestyle intervention program in overweight and obese adults. We recruited 26 participants from the Mayo Clinic Obesity Treatment Research Program between August 6, 2013, and September 12, 2013, to participate in a lifestyle intervention program for weight loss. Adults aged 18 to 65 years with a body mass index of 27 to 39.9 kg/m2 and able to provide informed consent were included in the study. Fecal stool samples were obtained at baseline and after 3 months. Loss of at least 5% of baseline weight after 3 months was defined as success. Clinical characteristics and gut microbial composition and function were compared between those who achieved at least 5% and those who achieved less than 5% weight loss. After 3 months, 9 of 26 participants lost at least 5% of their weight. The mean weight loss was 7.89 kg (95% CI, 6.46-9.32 kg) in the success group and 1.51 kg (95% CI, 0.52-2.49 kg) in the less than 5% weight loss group. An increased abundance of Phascolarctobacterium was associated with success. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to lose 5% body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.

Proton Pump Inhibitors: Review of Emerging Concerns.

First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.

Features of Adult Autoimmune Enteropathy Compared With Refractory Celiac Disease.

BACKGROUND & AIMS: Little is known about the features of immune-mediated non-celiac villous atrophies, such as autoimmune enteropathy (AIE). We investigated the demographic, clinical, and histologic features of adults with AIE compared to adults with refractory celiac disease type 1. We also report outcomes of treatment with open-label budesonide. METHODS: We performed a retrospective case-control of patients with AIE (n = 30) seen at the Mayo Clinic (in Rochester, Minnesota) from 2000 through 2015. Patients with refractory celiac disease type 1 who were treated with open-label budesonide served as controls (n = 42). Biopsy specimens were reviewed for all patients. We collected demographic, clinical, biochemical and histologic data from patients. We also collected data on responses to open-capsule budesonide from patients with AIE (available from 22 patients) and controls (available from 42 patients); the median duration of follow up was 28 months (range, 0-1421 months). RESULTS: Patients with AIE had a higher proportion of men (60%) and were younger (mean, 44 ± 18 years) than patients with refractory celiac disease type 1 (29% men; P = .002 and mean age, 57 ± 16 years; P = .007). A higher proportion of patients with AIE presented with chronic diarrhea (100%) and weight loss (90%) than patients with refractory celiac disease type 1 (71%; P < .001 and 71%; P = .05, respectively). Based on histologic analysis, there was no significant difference in degree of villous atrophy in intestinal tissues from patients with AIE vs controls (P = .68). However, a greater proportion of patients with RCD had increased intraepithelial lymphocytes (>40 per 100 epithelial cells in 100%) compared with patients with AIE (in 50%) (P = .003). Conventional therapy (systemic steroids) had failed in most patients with AIE (a complete clinical response was reported in only 7 patients) before treatment with open-capsule budesonide was initiated. A clinical response to open-capsule budesonide was reported for 85% of patients with AIE (50% complete response, 35% partial response) compared to 92% of controls (68% complete response, 24% partial response). CONCLUSIONS: In a retrospective study of 30 patients with AIE, followed for a median 28 months, we found this disease to have has distinct demographic, clinical, and histologic characteristics compared to refractory celiac disease type 1. Most patients with AIE (85%) have a clinical response to budesonide, all of whom were unsuccessfully treated with conventional therapies.

Tuberculosis of the gastrointestinal tract and associated viscera.

Tuberculosis involvement of the gastrointestinal tract, peritoneum, and associated viscera is an uncommon but well described entity. While peritoneal tuberculosis and tuberculous enteritis are more common, involvement of the esophagus, stomach, colon, rectum, anus, liver, bile ducts, gallbladder, and pancreas can occur. Diagnosis is challenging as cases often mimic neoplasm or inflammatory bowel disease. In this review we outline the pathogenesis, clinical presentation, diagnostic testing, and treatment strategies pertaining to such cases.

Clinical significance of incidental [18 F]FDG uptake in the gastrointestinal tract on PET/CT imaging: a retrospective cohort study.

BACKGROUND: The frequency and clinically important characteristics of incidental (18)F-fluorodeoxyglucose ([18 F]FDG) positron emission tomography (PET) uptake in the gastrointestinal tract (GIT) on PET/CT imaging in adults remain elusive. METHODS: All PET/CT reports from 1/1/2000 to 12/31/2009 at a single tertiary referral center were reviewed; clinical information was obtained from cases with incidental (18)F-FDG uptake in the GIT, with follow-up through October, 2012. RESULTS: Of the 41,538 PET/CT scans performed during the study period, 303 (0.7 %) had incidental GIT uptake. The most common indication for the PET/CT order was cancer staging (226 cases, 75 %), with 74 % for solid and 26 % for hematologic malignancies. Of those with solid malignancy, only 51 (17 %) had known metastatic disease. The most common site of GIT uptake was the colon, and of the 240 cases with colonic uptake, the most common areas of uptake were cecum (n = 65), sigmoid (n = 60), and ascending colon (n = 50). Investigations were pursued for the GIT uptake in 147 cases (49 %), whereas 51 % did not undergo additional studies, largely due to advanced disease. There were 73 premalignant colonic lesions diagnosed in 56 cases (tubular adenoma, n = 36; tubulovillous adenoma with low grade dysplasia, n = 27; sessile serrated adenoma, n = 4; tubulovillous adenoma with high grade dysplasia, n = 3; villous adenoma, n = 3), and 20 cases with newly diagnosed primary colon cancer. All 20 (100 %) patients with malignant colonic lesions had a focal pattern of [18 F]FDG uptake. Among cases with a known pattern of [18 F]FDG uptake, 98 % of those with premalignant lesions had focal [18 F]FDG uptake. Eighteen (90 %) of the cases with newly diagnosed colon cancer were not known to have metastatic disease of their primary tumor. Areas of incidental uptake in the ascending colon had the greatest chance (42 %) of being malignant and premalignant lesions than in any other area. CONCLUSION: Focality of uptake is highly sensitive for malignant and premalignant lesions of the GIT. In patients without metastatic disease, incidental focal [18]FDG uptake in the GIT on PET/CT imaging warrants further evaluation.

Gut Microbiota: Modulation of Host Physiology in Obesity.

Many factors are involved in weight gain and metabolic disturbances associated with obesity. The gut microbiota has been of particular interest in recent years, since both human and animal studies have increased our understanding of the delicate symbiosis between the trillions of microbes that reside in the GI tract and the host. It has been suggested that disruption of this mutual tolerance may play a significant role in modulating host physiology during obesity. Environmental influences such as diet, exercise, and early life exposures can significantly impact the composition of the microbiota, and this dysbiosis can in turn lead to increased host adiposity via a number of different mechanisms. The ability of the microbiota to regulate host fat deposition, metabolism, and immune function makes it an attractive target for achieving sustained weight loss.

Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice.

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8-12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups (P < 0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions (P < 0.05). Contrary to our hypothesis, the α-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED (P < 0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region.

Gastric antral injections of botulinum toxin delay gastric emptying but do not reduce body weight.

BACKGROUND & AIMS: Gastric injections of botulinum toxin A (BTA) have been reported to delay gastric emptying, increase satiation, and reduce body weight, but there are few data from randomized, placebo-controlled studies. METHODS: We enrolled 60 obese participants in a 24-week, double-blind, randomized, placebo-controlled, concealed allocation trial to compare the effects of gastric antral injections of BTA (100, 300, or 500 U) and saline placebo. The study was conducted at an outpatient clinical research unit. Participants were given one set of injections of BTA or placebo into the gastric antral muscularis propria by using endoscopic ultrasound guidance. Gastric emptying of solids was measured by scintigraphy; we also measured body weight, satiation (maximum tolerated volume in a caloric liquid drink test), calorie intake (by food frequency questionnaire), gastrointestinal symptoms, and psychological aspects of eating behavior (by rating scale). RESULTS: Compared with baseline values, 2 weeks after injections, the mean half-time for gastric emptying of solids increased by 0.8, 14, 24, and 14 minutes among subjects given placebo, 100, 300, or 500 U BTA, respectively (P = .24 overall, P = .04 for the group given 300 U vs placebo); 16 weeks after the injections, mean body weights were reduced by 2.2, 0.2, 2.3, and 3.0 kg in these groups, respectively. There were no statistically significant differences in mean body weight change, satiation volume, caloric intake, gastrointestinal symptoms, or psychological aspects of eating behavior among groups. CONCLUSIONS: Gastric antral injections of BTA may delay gastric emptying at a dose of 300 U but do not cause early satiety, altered eating behaviors, or loss of body weight. Clinicaltrials.gov identifier: NCT00976443.

Coingestion of whey protein and casein in a mixed meal: demonstration of a more sustained anabolic effect of casein.

When consumed separately, whey protein (WP) is more rapidly absorbed into circulation than casein (Cas), which prompted the concept of rapid and slow dietary protein. It is unclear whether these proteins have similar metabolic fates when coingested as in milk. We determined the rate of appearance across the splanchnic bed and the rate of disappearance across the leg of phenylalanine (Phe) from coingested, intrinsically labeled WP and Cas. Either [¹5N]Phe or [¹³C-ring C6]Phe was infused in lactating cows, and the labeled WP and Cas from their milk were collected. To determine the fate of Phe derived from different protein sources, 18 healthy participants were studied after ingestion of one of the following: 1) [¹5N]WP, [¹³C]Cas, and lactose; 2) [¹³C]WP, [¹5N]Cas, and lactose; 3) lactose alone. At 80-120 min, the rates of appearance (R(a)) across the splanchnic bed of Phe from WP and Cas were similar [0.068 ± 0.010 vs. 0.070 ± 0.009%/min; not significant (ns)]. At time 220-260 min, Phe appearance from WP had slowed (0.039 ± 0.008%/min, P < 0.05) whereas Phe appearance from Cas was sustained (0.068 ± 0.013%/min). Similarly, accretion rates across the leg of Phe absorbed from WP and Cas were not different at 80-120 min (0.011 ± 0.002 vs. 0.012 ± 0.003%/min; ns), but they were significantly lower for WP (0.007 ± 0.002%/min) at 220-260 min than for Cas (0.013 ± 0.002%/min) at 220-260 min. Early after meal ingestion, amino acid absorption and retention across the leg were similar for WP and Cas, but as rates for WP waned, absorption and assimilation into skeletal muscle were better retained for Cas.

Endoscopic ultrasound-guided gastric botulinum toxin injections in obese subjects: a pilot study.

BACKGROUND: Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects. METHODS: Open label study of ten healthy, obese adults (age = 29-49 years, body mass index = 31-54 kg/m(2)) who received 100 U (n = 4) or 300 U (n = 6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight. RESULTS: For the entire cohort, MTV decreased from 1,380 cc (range: 474-2,014) at baseline to 620 cc (range: 256-1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p = 0.03). Average body weight loss was 4.9 (+/-6.3) kg after 16 weeks. Gastric emptying T(1/2) was prolonged in the 300 U BTA group, but not significantly different from baseline (p = 0.17). BTA injections were well tolerated without significant adverse effects. CONCLUSION: EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.