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Mattis Bekkelund,1,2 Dag A Sangnes,2– 4 Eirik Søfteland,3– 5 Lars Aabakken,1,6 Martin Biermann,4,7 Elisabeth K Steinsvik,2,4,8 Trygve Hausken,2,8 Georg Dimcevski,4,8 Jan Gunnar Hatlebakk2– 4 1Department of Clinical Medicine, University of Oslo, Oslo, Norway; 2Norwegian Competence Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway; 3Department of Medicine, Haukeland University Hospital, Bergen, Norway; 4Department of Clinical Medicine, University of Bergen, Bergen, Norway; 5Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; 6Department of Transplantation Medicine, Section for Gastroenterology, Oslo University Hospital, Oslo, Norway; 7Centre for Nuclear Medicine and PET, Department of Radiology, Haukeland University Hospital, Bergen, Norway; 8National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, NorwayCorrespondence: Mattis BekkelundNorwegian Competence Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, 5021, NorwayTel +47 48 18 68 97Email mattis.bekkelund@hotmail.comObjective: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule.Patients and Methods: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI).Results: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (rs = − 0.31, p = 0.007), small bowel (rs = − 0.41, p < 0.001) and colonic (rs = − 0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (rs = − 0.81, p < 0.001) and mean stomach pressure (rs = − 0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (rs = − 0.77, p < 0.001) and colon (rs = − 0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (rs = − 0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (rs = − 0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times.Conclusion: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.Keywords: gastric emptying, gastrointestinal motility, gastroparesis, gastroparesis-like syndrome, small bowel, wireless motility capsule, scintigraphy

Background: The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients.Aims: To investigate a possible abnormality in the colonic endocrine cells of IBS patients.Methods: A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis.Results: Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification.Conclusion: The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) is a common chronic digestive disease that affects people in different communities at different rates. Because of the absence of a validated Arabic tool to assess GERD symptoms, this study aimed to validate and culturally adapt the GERD questionnaire (GerdQ) tool to Arabic speakers., Methods: Patients referred for pH testing with symptoms suggestive of GERD were recruited. A cross-sectional study was conducted from March 2023 to April 2023 by administering the Arabic GERD questionnaire (Ar-GerdQ) tool on two different occasions and comparing it with the short-form leeds dyspepsia questionnaire and the Reflux Symptom Index to establish reliability and construct validity., Results: A total of 52 participants were included in the study. The results of the internal consistency analysis of the Ar-GerdQ indicate that the test has good reliability, with a Cronbach's alpha coefficient of 0.86 (95% CI: 0.75-0.91). Significant positive correlations with the short form leeds dyspepsia questionnaire (r = 0.59, P < 0.001, 95% CI: 0.29-0.78) and the reflux symptom index (r = 0.47, P = 0.01, 95% CI: 0.13-0.71) were demonstrated. Moreover, the intraclass correlation coefficient value was 0.60 ( P < 0.001, 95% CI: 0.28-0.77), indicating a substantial level of agreement between the measurements., Conclusions: Our findings indicate that the Ar-GerdQ is useful for assessing reflux disease symptoms among Arabic speakers. Effective utilization of Ar-GerdQ will reduce unnecessary endoscopic requests in primary care settings., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures (www.clinicaltrials.gov: NCT04236843)., Competing Interests: Declaration of competing interest M.E.S and JGH have nothing to disclose. OHG has received speaker honoraria from Bracco, GE Healthcare, Takeda AS, Ferring AS, Allergan, and Janssen-Cilag. He has served as consultant for Bracco, GE Healthcare, Takeda and Samsung., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), contributes to substantial morbidity. Understanding the intricate interplay between dietary factors and the incidence and progression of IBD is essential for developing effective preventative and therapeutic strategies. This umbrella review comprehensively synthesizes evidence from systematic reviews and meta-analyses to evaluate these complex associations. Dietary factors associated with an increased incidence and/or progression of IBD include a high intake of red and processed meat, other processed foods, and refined sugars, together with a low intake of vegetables, fruits, and fiber. For most other food groups, the results are mixed or indicate no clear associations with IBD, CD, and UC. Some differences seem to exist between UC and CD and their risk factors, with increased intake of dietary fiber being inversely associated with CD incidence but not clearly associated with UC. Dietary fiber may contribute to maintaining the gut epithelial barrier and reduce inflammation, often through interactions with the gut microbiota. This seems to play an important role in inflammatory mechanisms in the gut and in IBD incidence and progression. Diets low in fermentable saccharides and polyols can alleviate symptom burden, but there are concerns regarding their impact on the gut microbiota and their nutritional adequacy. Mediterranean diets, vegetarian diets, and a diet low in grains, sugars, and lactose (specific carbohydrate diet) are also associated with lower incidence and/or progression of IBD. The associations of dietary patterns are mirrored by inflammatory biomarkers. IBD is typically treated pharmaceutically; however, many patients have a suboptimal response to medical treatments. The findings from this umbrella review could provide evidence for nutritional counseling and be a valuable addition to traditional treatment plans for IBD. This systematic review was registered at PROSPERO as CRD440252., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Faecal microbiota transplantation (FMT) performed with a proper protocol is a safe treatment for IBS that has high efficacy and durable effects. Females have been reported to respond better than males to FMT. The present study aimed at determining whether increasing the transplant dose or repeating FMT improve the responses of males to FMT., Methods: This study included 186 IBS patients (131 females and 55 males) who were randomized at a 1:1:1 ratio to receive 90 g of donor faeces once into the large intestine, once into the small intestine or twice into the small intestine. Patients completed five questionnaires that assessed their symptoms and quality of life, and provided faecal samples at baseline and at 3, 6 and 12 months after FMT. The faecal bacterial profile and dysbiosis index were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9., Results: The response rates to FMT at all observation times did not differ significantly between females and males regardless of the transplant administration route or whether it was repeated. Faecal Alistipes levels were higher in females than in males at baseline and increased in both females and males after FMT. In the repeated group, the Alistipes levels did not differ between females and males after FMT., Conclusions: Increasing the transplant dose and repeating FMT results in the responses of male IBS patients to FMT reaching those of females regardless of the administration route. Alistipes spp. levels appear to play a role in this improvement.www.clinicaltrials.gov (NCT04236843).

Background: Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS., Aims: The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference., Methods: This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16 S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9., Results: There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS., Conclusions: There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. ( www., Clinicaltrials: gov : NCT04236843)., (© 2024. The Author(s).)

Background: A previous study that introduced a Fecal microbiota transplantation (FMT) protocol with a high efficacy applied a combination of favorable factors., Aims: The present study aimed to evaluate some of these factors., Methods: This study included 186 patients with IBS randomized 1:1:1 into transplant administered to the colon (single LI), to the duodenum (single SI), or to the duodenum twice with a 1-week interval (repeated SI). The patients provided a fecal sample and were asked to complete five questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9., Results: The response rate was significantly higher in single SI than in single LI at 12 months after FMT. Symptoms and quality of life improved in all the treated groups at all time intervals after FMT. The abdominal symptoms were significantly reduced and the quality of life improved for repeated SI compared with for single SI. DI significantly decreased in all the treated groups at all observation times after FMT. The bacterial profiles changed in all groups at all observation intervals. However, these changes differed between single LI and single SI/repeated SI., Conclusion: Administrating transplant to the small intestine had a long-term higher response rate than that administrated to the large intestine, and led to long-term colonization of beneficial bacteria. Repeating FMT had more effect on symptoms and quality of life than a single FMT. (www., Clinicaltrials: gov: NCT04236843)., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background and Aims: Per oral endoscopic myotomy (POEM) has become an established treatment for achalasia, but no Scandinavian studies with long-term follow-up exist. This study from a tertiary referral center in Norway investigates the short-, mid-, and long-term feasibility, safety, efficacy, and complications of POEM., Methods: Prospective data from the first 84 patients who underwent POEM from 2014 to 2019 were analyzed. The median follow-up time was 44 months. Clinical success was defined as the Eckardt score (ES) ⩽3, and reflux as pathological if the acid exposure time (pH < 4) was more than 6%. ES was used for symptom evaluation before, and at 6, 12, and up to 64 months after POEM., Results: A total of 50 males and 34 females were included. A total of 43 (51%) were treatment naïve, 24 (28.6%) had been previously treated with botulinum toxin, pneumatic balloon dilatation, or both, and 17 (20.2%) were previously treated with Heller's myotomy. The median post-POEM ES at 12 months was 1 (0-9), compared to pre-POEM 7 (4-12) (p < 0.01). At 12 months after POEM, clinical success persisted in 74 patients (88.1%). Clinical success was the highest for patients who were naïve to treatment, 41/43 (95%), and lower for those previously treated with Heller's myotomy 12/17 (70.6%). Long-term follow-up at 5-6 years of 42 patients showed a clinical success rate of 94%. We experienced adverse events in five patients (6%). Post-POEM pathological reflux was found in 46% (28/61). After 3-4 years, the median ES was 1, and after 5-6 years, it was 2., Conclusion: POEM was safe and relieved the symptoms of achalasia significantly and persistently. The procedure had a better outcome in treatment naïve than previously treated patients. However, POEM is associated with significantly increased esophageal acid exposure., Twitter Summary: Norwegian single-center study: POEM had a clinical success rate of 94% after 5-6 years since its introduction at the center in 2014, providing a safe and effective treatment for achalasia.

Background & Aims: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects., Methods: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed 5 questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index were analyzed using 16S ribosomal RNA gene polymerase chain reaction DNA amplification/probe hybridization covering the V3 to V9 regions., Results: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The dysbiosis index decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded., Conclusions: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events. This study was registered at www., Clinicaltrials: gov (NCT03822299)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension ( n = 17), donor-FMT ( n = 11), or placebo ( n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.

Objectives: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms., Materials and Method: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes., Results: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum , and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT., Conclusion: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.

Background: Fecal microbiota transplantation (FMT) interventions have recently been advocated to not succeed in every irritable bowel syndrome (IBS) patient, since the outcome of FMT varies with the IBS subset. This study investigated the factors potentially affecting FMT response using the same patient cohort used in our previous study., Methods: This study included 109 patients who received allogenic FMT. Patients completed five questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT. Patients also provided fecal samples at baseline and 1 month after FMT. The fecal bacterial profile and dysbiosis index (DI) were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. Response to FMT was defined as a decrease of ≥50 points in the total IBS-SSS score after FMT., Results: An IBS patient's response or nonresponse to FMT was not determined by age, IBS duration, IBS subtype, IBS symptoms, fatigue, quality of life, or DI. There were more male nonresponders than responders, and the fluorescence signals of Alistipes were lower in nonresponders than in responders., Conclusions: We concluded that IBS patients who are male and/or have low fecal Alistipes levels are most likely to not respond to FMT treatment. Whether low fecal Alistipes levels could be used as a marker for predicting the outcome of FMT remains to be determined. www., Clinicaltrials: gov (NCT03822299)., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment., Methods: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1 year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography., Results: There was a persistent response to FMT at 1 year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1 year and 3 months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1 year compared with after 3 months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs., Conclusions: Most of the IBS patients maintained a response at 1 year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1 year than after 3 months. www.clinicaltrials.gov (NCT03822299)., (© 2021 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising., Purpose: The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients., Methods: A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS., Key Results: Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect., Conclusions and Inferences: The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting., (© 2021 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: In the following review we outline how ultrasound can be used to measure physiological processes in the gastrointestinal tract., Approach: We have investigated the potential of ultrasound in assessing gastrointestinal physiology including original research regarding both basic methodology and clinical applications., Main Results: Our main findings show the use of ultrasound to study esophageal motility, measure volume and contractility of the stomach, assess motility, wall thickness, and perfusion of the small bowel, and evaluate wall vascularization and diameters of the large bowel., Significance: Ultrasound is a widely accessible technology that can be used for both scientific and clinical purposes. Being radiation-free and user friendly, the examination can be frequently repeated enabling longitudinal studies. Furthermore, it does not influence normal GI physiology, thus being useful to estimate motility and subtle changes in physiology. Accordingly, ultrasound scanning and physiological measurements may make a big difference for the scientist and the doctor; and for the patients who receive an efficient work-up.

Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein, n = 15) or placebo (0 g protein, n = 15). We observed no effect on fasting or postprandial levels of acylated ghrelin, fasting levels of adiponectin ( p = 0.089) or leptin ( p = 0.967) after supplementation with CPH, compared to placebo. Overall, our study showed that 8 weeks supplementation with a low dose of CPH in subjects with MetS had no effect on satiety hormones or most of the inflammatory markers, but the levels of high-sensitivity C-reactive protein were statistically significantly different in the CPH-group compared to placebo group. The robustness and clinical relevance of these findings should be explored in future studies with a larger sample size.

Irritable bowel syndrome (IBS) affects ~12% of the global population. Although the etiology of IBS is not completely understood, several factors are known to serve a pivotal role in its pathophysiology, including genetic factors, diet, the intestinal microbiota, gastrointestinal endocrine cells and low‑grade inflammation. Musashi‑1 is expressed by stem cells and their early progeny, and is used as a stem cell marker. The low density of intestinal endocrine cells in patients with IBS is thought to be caused by decreased numbers of intestinal stem cells and their differentiation into enteroendocrine cells. The present study employed Musashi‑1 as a marker to detect stem cells in the stomach of 54 patients with IBS and 51 healthy subjects. The patients and controls underwent standard gastroscopy, and biopsy samples were taken from the corpus and antrum. Immunohistochemical staining of gastrin, somatostatin and Mushasi‑1 was carried out and semi‑quantified by computerized image analysis. The density (number of positive cells/mm2 epithelium) of gastrin‑positive cells in the controls and patients with IBS were 337.9±560 and 531.0±908 (median ± range; P<0.0001), respectively. For somatostatin‑positive cells, the density reached 364.4±526.0 in the healthy controls and 150.7±514.0 in patients with IBS (P<0.0001). The density of Musashi‑1‑positive cells was defined as the number of cells per gastric or pyloric gland neck. In the corpus, Musashi‑1‑positive cells density reached 3.0±7.0 in the corpus of the healthy controls and 3.8±7.7 in the patients with IBS. Moreover, the corresponding values in the antrum were 6.0±6.0 and 6.0±6.0, respectively. The Musashi‑1‑positive cell density did not differ significantly between the controls and patients with IBS in the corpus or antrum (P=0.4 and 0.3, respectively). These findings indicated that changes in the stomach endocrine cells observed in patients with IBS may not be explained by an abnormality in stem cells like those found in the small and large intestines of these patients.

Introduction: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS., Methods: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection., Discussion: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown., Trial Registration Number: NCT04296552 (ClinicalTrials.gov).

The risk of cardiovascular diseases and type 2 diabetes mellitus are increased in subjects with metabolic syndrome (MetS), and hydrolyzed fish protein may have favorable effects on metabolic health. Here, we investigated the effect of 8 weeks supplementation with 4 g of cod protein hydrolysate (CPH) on glucose metabolism, lipid profile and body composition in individuals with MetS in a double-blind, randomized intervention study with a parallel-group design. Subjects received a daily supplement of CPH ( n = 15) or placebo ( n = 15). Primary outcomes were serum fasting and postprandial glucose levels. Secondary outcomes were fasting and postprandial insulin and glucagon-like peptide 1 (GLP-1), fasting lipid concentrations and body composition. No difference was observed between CPH and placebo for insulin, glucose or GLP-1 after 8 weeks intervention. Fasting triacylglycerol decreased in both the CPH group and placebo group, with no change between groups. Fasting total cholesterol and low-density lipoprotein cholesterol decreased significantly within both groups from baseline to study end, but no difference was observed between the two groups. In conclusion, supplementing with a low dose of CPH in subjects with MetS for 8 weeks had no effect on fasting or postprandial levels of insulin, glucose or GLP-1, lipid profile or body composition., Competing Interests: The authors declare no conflict of interest.

Objective: Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings., Design: This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1 month following FMT., Results: Responses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms., Conclusions: FMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose. Trial registration www.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder of unknown aetiology for which there is no effective treatment. Although IBS does not increase mortality, it reduces the quality of life and is an economic burden to both the patients themselves and society as a whole. Peptide YY (PYY) is localized in endocrine cells located in the ileum, colon and rectum. The concentration of PYY and the density of PYY cells are decreased in both the colon and rectum but unchanged in the ileum of patients with IBS. The low density of PYY cells in the large intestine may be caused by a decreased number of stem cells and their progeny toward endocrine cells. PYY regulates the intestinal motility, secretion and absorption as well as visceral sensitivity via modulating serotonin release. An abnormality in PYY may therefore contribute to the intestinal dysmotility and visceral hypersensitivity seen in IBS patients. Diet management involving consuming a low-FODMAP diet restores the density of PYY cells in the large intestine and improves abdominal symptoms in patients with IBS. This review shows that diet management appears to be a valuable tool for correcting the PYY abnormalities in the large intestine of IBS patients in the clinic., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A large proportion of older adults are affected by impaired glucose metabolism. Previous studies with fish protein have reported improved glucose regulation in healthy adults, but the evidence in older adults is limited. Therefore, we wanted to assess the effect of increasing doses of a cod protein hydrolysate (CPH) on postprandial glucose metabolism in older adults. The study was a double-blind cross-over trial. Participants received four different doses (10, 20, 30 or 40 mg/kg body weight (BW)) of CPH daily for 1 week with 1-week washout periods in between. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose and insulin in 20 min intervals for 120 min. The secondary outcome was postprandial response in plasma glucagon-like peptide 1 (GLP-1). Thirty-one subjects aged 60-78 years were included in the study. In a mixed-model statistical analysis, no differences in estimated maximum value of glucose, insulin or GLP-1 were observed when comparing the lowest dose of CPH (10 mg/kg BW) with the higher doses (20, 30 or 40 mg/kg BW). The estimated maximum value of glucose was on average 0·28 mmol/l lower when the participants were given 40 mg/kg BW CPH compared with 10 mg/kg BW ( P = 0·13). The estimated maximum value of insulin was on average 5·14 mIU/l lower with 40 mg/kg BW of CPH compared with 10 mg/kg BW ( P = 0·20). Our findings suggest that serum glucose and insulin levels tend to decrease with increasing amounts of CPH. Due to preliminary findings, the results require further investigation., (© The Author(s) 2019.)

Background: Fish protein hydrolysates are suggested to contain bioactive sequences capable of affecting metabolic pathways involved in the regulation of glucose metabolism and body weight when consumed in low doses. Modulation of the appetite-regulating hormone ghrelin may explain suppression of insulin secretion and weight loss observed in previous studies with fish protein hydrolysates., Objective: This study aimed to assess the effect of a single, low dose of cod protein hydrolysate (CPH) before a breakfast meal on postprandial acylated ghrelin concentration and sensations associated with appetite in healthy subjects., Design: In this explorative trial with a crossover design, 41 healthy individuals (15 males and 26 females, age 51 ± 6 years) completed 2 study days separated by 4-7 days of washout. On both study days, a test drink containing 20 mg CPH or casein (control) per kg body weight was given immediately before a standardized breakfast meal. Acylated ghrelin concentrations were measured before test drink/breakfast (baseline) and at time 0, 20, 40, 80, and 180 min postprandially. Sensations associated with appetite were measured by a Visual Analog Scale (100 mm) at baseline and 0, 20, 40, and 180 min postprandially., Results: Statistically, no difference was observed between CPH and control for postprandial acylated ghrelin concentrations (mean difference geometric mean: 1.05 pg/mL, 95% confidence interval [CI]: 0.97-1.13, P = 0.266), or between the total area under the curve (tAUC) for acylated ghrelin after CPH (tAUC = 17518 pg/mL × min, 95% CI: 0-47941) and control (tAUC = 17272 pg/mL × min, 95% CI: 0-48048, P = 0.991). No differences were found between CPH and control for sensation of appetite, according to tAUC of postprandial scores for satiety ( P = 0.794) and the feeling of fullness ( P = 0.996)., Conclusion: We did not find an effect of a single dose of CPH on postprandial concentrations of acylated ghrelin or sensations related to feeling of hunger, compared to control. Further studies should aim to evaluate the effect of a supplement with CPH given daily over a period of time., Competing Interests: Einar Lied is professor emeritus at the University of Bergen, Bergen, Norway, and former Scientific Advisor in Firmenich Bjørge Biomarin AS (Ellingsøy, Ålesund, Norway), where he holds a royalty agreement. The other authors declare no conflict of interest., (© 2019 Hanna Fjeldheim Dale et al.)

Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.

Irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD) overlap. It is not clear whether GERD is caused by non‑erosive esophagitis, or erosive esophagitis. The Rome criteria are not widely used for the diagnosis of IBS in the clinic. In total, 1,489 IBS patients without red flags were included in the present retrospective study. They comprised of 1,331 females and 158 males with a mean age of 51 years. The diagnosis of IBS was verified by endoscopic and histopathological examinations. Whereas erosive esophagitis occurred in 97% of patients, only 66% had GERD symptoms. Endoscopy and histopathological examinations revealed that 1.4% of the IBS patients with diarrhea as the predominant symptom had other organic gastrointestinal diseases: 0.3% with celiac disease, 0.2% with Crohn's disease, 0.07% with ulcerative colitis, 0.6% with microscopic colitis, and 0.2% with colon cancer. Applying the Rome III criteria produced a sensitivity of 100% [95% confidence intervals (CI)=99.8‑100.0%] a specificity of 98.7% (95% CI=98.0‑99.2%), a positive likelihood ratio of 76.9%, and a negative likelihood ratio of 0%. IBS is associated with erosive esophagitis. Applying Rome III criteria without red flags and history, was effective in diagnosing IBS. Celiac disease and microscopic colitis should be considered as alternative diagnoses.

Background: Faecal microbiome transplantation (FMT) appears to be an effective method for treating irritable bowel syndrome (IBS) patients. However, it is not clear if a high transplant dose and/or repeating FMT are/is needed to ensure a response. The present study was undertaken to clarify this matter., Methods: Ten IBS patients who did not respond to a 30-g transplant subsequently received a 60-g transplant into the duodenum via a gastroscope. The patients provided faecal samples before and 1 month after FMT. They completed five questionnaires measuring symptoms, fatigue and quality of life at baseline and then at 2 weeks, 1 month and 3 months after FMT. The dysbiosis index (DI) was measured using the GA-map Dysbiosis Test ® ., Results: Seven patients (70%) responded to the 60-g transplant, with significant clinical improvements in the abdominal symptoms, fatigue and quality of life in 57%, 80% and 67% of these patients. The 60-g transplant also reduced the DI., Conclusion: FMT is an effective treatment for IBS. A high-dose transplant and/or repeated FMT increase the response rate and the intensity of the effects of FMT.

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.

Purpose: Delayed gastric emptying is present in patients with functional dyspepsia (FD), diabetes mellitus, and neurological diseases. Diet may affect gastric emptying symptoms in patients with FD. We sought to determine the extent to which gastric emptying and symptoms of dyspepsia are influenced by caloric content in healthy subjects using ultrasonography., Materials and Methods: 32 healthy volunteers were given 2 meals with different caloric content in random order. Gastric emptying was determined using ultrasonography to measure antral area when fasting, and postprandially at intervals of 0, 10, 20, and 30 min. Dyspeptic symptoms including discomfort, nausea, and fullness were graded., Results: The antral area following a high-caloric meal compared to a low-caloric meal was significantly increased at 0, 10, 20, and 30 min (P=0.0203,<0.0001<0.0001,<0.0001, respectively), as was the median fullness (P<0.0048, 0.0001, 0.0009, 0.0001, respectively) measured at the same time points. There was a weak correlation (r2=0.1, P<0.0001) between the antral area and subjective fullness. No differences between gastric emptying in males and females were found., Conclusion: The caloric content of a meal influences gastric emptying. Using ultrasonography to measure the antral area helps us to assess gastric emptying and therefore to assess patients with functional dyspepsia.

The increased prevalence of lifestyle diseases, such as the metabolic syndrome and type 2 diabetes mellitus (T2DM), calls for more knowledge on dietary treatments targeting the specific metabolic pathways involved in these conditions. Several studies have shown a protein preload before a meal to be effective in lowering the postprandial glycaemic response in healthy individuals and patients with T2DM. The aim of the present study was to assess the effect of a marine protein hydrolysate (MPH) from Atlantic cod ( Gadus morhua ) on postprandial glucose metabolism in healthy, middle-aged to elderly subjects. This double-blind cross-over trial ( n 41) included two study days with 4-7 d wash-out in between. The intervention consisted of 20 mg of MPH (or casein as control) per kg body weight given before a breakfast meal. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose, insulin and plasma glucagon-like peptide 1 (GLP-1) in 20 min intervals for 180 min. In a mixed-model regression analysis, no differences were observed between MPH and control for postprandial glucose concentration (mean difference: -0·04 (95 % CI -0·17, 0·09) mmol/l; P = 0·573) or GLP-1 concentration (mean difference between geometric means: 1·02 (95 % CI 0·99, 1·06) pmol/l; P = 0·250). The postprandial insulin concentration was significantly lower after MPH compared with control (mean difference between geometric means: 1·067 (95 % CI 1·01, 1·13) mIU/l; P = 0·032). Our findings demonstrate that a single dose of MPH before a breakfast meal reduces postprandial insulin secretion, without affecting blood glucose response or GLP-1 levels, in healthy individuals. Further studies with repeated dosing and in target groups with abnormal glucose control are warranted.

Background: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS., Material and Methods: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression., Results: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects., Conclusions: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks., Trial Registration: ClinicalTrials.gov ID: NCT03333291., Competing Interests: The authors have declared that no competing interests exist.

Background: In achalasia, muscle spasm may involve the proximal esophagus. When the muscle spasm is located in the proximal esophagus, conventional per oral endoscopic myotomy (POEM) may not be sufficient to relieve symptoms. In this paper, we describe retrograde endoscopic myotomy (REM) as a novel approach to perform myotomy of the proximal esophagus, with the application of a navigation tool for anatomical guidance during REM. We aim to evaluate the feasibility and safety of REM and usefulness of the navigation during REM., Method: A 42-year-old male with type III achalasia who was treated with laparoscopic myotomy with fundoplication, multiple pneumatic balloon dilations, Botox injections and anterior POEM of the middle and distal esophagus without symptomatic effect. Repeated high-resolution- manometry (HRM) revealed occluding contractions of high amplitude around and above the aortic arch. A probe-based real-time electromagnetic navigation platform was used to facilitate real-time anatomical orientation and to evaluate myotomy position and length during REM., Results: The navigation system aided in identifying the major structures of the mediastinum, and position and length of the myotomy. Twelve weeks after REM, the Eckardt score fell from seven at baseline seven to two. We also observed improvement with reduction of the pressure at the level of previous spasms in the proximal esophagus from 124 mmHg to 8 mmHg on HRM., Conclusion: REM makes the proximal esophagus accessible for endoscopic myotomy. Potential indication for REM is motility disorders in the proximal esophagus and therapy failure after POEM., (© 2017 John Wiley & Sons Ltd.)

Background: Gastric accommodation to a meal may be important in the pathogenesis of upper gastrointestinal disorders, but has been difficult to investigate in a minimally invasive fashion., Methods: We studied gastric and lower esophageal physiology during food intake, combining transabdominal ultrasound, multichannel high-resolution impedance-manometry (HRIM) and a symptom questionnaire. A HRIM catheter was distally positioned at incisura angularis and 300 mL saline with 75 g glucose was ingested. Target variables were recorded for 30 min after fluid intake., Key Results: Fifteen healthy subjects' participated (11W/4M, median age 23.8 y) and all accepted the meal with few symptoms. At incisura angularis maximum change in pressure from pre-intake values was -7.4 mmHg after 60 s (P < .0001), rising to pre-intake values within 20 min. The corresponding area increased significantly from pre-intake values of 8.0 cm 2 to 14.1 cm 2 shortly after intake (P = .0012), peaked at 5 min and slowly decreased towards 30 min. The corresponding maximum change in stress from pre-intake pressure values was -59.2 mmHg shortly after (P < .0001), reaching pre-intake values within 20 min. Strain rose from 0 shortly before to 0.36 shortly after (P < .0001), peaking at 5 min. At incisura angularis, fullness was positively correlated with area and to strain, while fullness, area, and stress were negatively correlated with pressure., Conclusions & Inferences: The multimodal method enabled assessment of the gastric accommodation reflex, stress and strain in the stomach. It triggered few symptoms in healthy volunteers. We propose it to be a more physiological replacement of the barostat technique., (© 2017 John Wiley & Sons Ltd.)

Background: Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD)., Methods: Twenty patients (14F/6M, age range: 21-62 years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0 g gluten) for 4 days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure., Key Results: Collectively the whole group reported the most severe symptoms after placebo (P = .012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P = .029)., Conclusions and Inferences: The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms., (© 2018 John Wiley & Sons Ltd.)

Objectives: The prevalence, gender distribution and clinical presentation of IBS differ between Asian and Western countries. This study aimed at studying and comparing enteroendocrine, Musashi 1 (Msi 1) and neurogenin 3 (neurog 3) cells in Thai and Norwegian IBS patients., Material and Methods: Thirty Thai and 61 Norwegian IBS patients as well as 20 Thai and 24 Norwegian controls were included. Biopsy samples were taken from each of the sigmoid colon and the rectum during a standard colonoscopy. The samples were immunostained for serotonin, peptide YY, oxyntomodulin, pancreatic polypeptide, somatostatin, Msi 1 and neurog 3. The densities of immunoreactive cells were determined with computerized image analysis., Results: The densities of several enteroendocrine cell types were altered in both the colon and rectum of both Thai and Norwegian IBS patients. Some of these changes were similar in Thai and Norwegian IBS patients, while others differed., Conclusions: The findings of abnormal densities of the enteroendocrine cells in Thai patients support the notion that enteroendocrine cells are involved in the pathophysiology of IBS. The present observations highlight that IBS differs in Asian and Western countries, and show that the changes in large-intestine enteroendocrine cells in Thai and Norwegian IBS patients might be caused by different mechanisms.

Inflammatory bowel disease (IBD) is a chronic recurrent condition whose etiology is unknown, and it includes ulcerative colitis, Crohn's disease, and microscopic colitis. These three diseases differ in clinical manifestations, courses, and prognoses. IBD reduces the patients' quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal (GI) neuroendocrine peptides/amines (NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover, the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD, and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin, the neuropeptide Y family, and substance P are proinflammatory, while the chromogranin/secretogranin family, vasoactive intestinal peptide, somatostatin, and ghrelin are anti-inflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD, and are candidate targets for treatments of this disease., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Objective: Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients., Methods: Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin-eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis., Results: In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls., Conclusions: The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.