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Background: Probiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown., Methods: A multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes., Results: Thirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms., Limitations: This study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up., Conclusion: Probiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neural mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments., Competing Interests: Conflict of interest The authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The rapid increase in sugar consumption is associated with various negative metabolic and inflammatory effects; therefore, alternative sweeteners become of interest. The aim of this study was to investigate the metabolic effects and safety aspects of acute D-allulose and erythritol on glucose, insulin, ghrelin, blood lipids, uric acid, and high-sensitive C-reactive protein (hsCRP). In three study visits, 18 healthy subjects received an intragastric administration of 25 g D-allulose or 50 g erythritol, or 300 mL tap water (placebo) in a randomized, double-blind and crossover order. To measure the aforementioned parameters, blood samples were drawn at fixed time intervals. Glucose and insulin concentrations were lower after D-allulose compared to tap water ( p = 0.001, d z = 0.91 and p = 0.005, d z = 0.58, respectively); however, Bayesian models show no difference for insulin in response to D-allulose compared to tap water, and there was no effect after erythritol. An exploratory analysis showed that ghrelin concentrations were reduced after erythritol compared to tap water ( p = 0.026, d z = 0.59), with no effect after D-allulose; in addition, both sweeteners had no effect on blood lipids, uric acid and hsCRP. This combination of properties identifies both sweeteners as excellent candidates for effective and safe sugar alternatives.

Background: There is a growing consensus that sugar consumption should be reduced and the naturally occurring, low-calorie sweeteners xylitol and erythritol are gaining popularity as substitutes, but their effect on brain circuitry regulating appetite is unknown., Aim: The study's objective was to examine the effects of the two sweeteners on cerebral blood flow (rCBF) and resting functional connectivity in brain networks involved in appetite regulation, and test whether these effects are related to gut hormone release., Methods: The study was performed as a randomized, double-blind, placebo-controlled, cross-over trial. Twenty volunteers received intragastric (ig) loads of 50g xylitol, 75g erythritol, 75g glucose dissolved in 300mL tap water or 300mL tap water. Resting perfusion and blood oxygenation level-dependent data were acquired to assess rCBF and functional connectivity. Blood samples were collected for determination of CCK, PYY, insulin and glucose., Results: We found: (i) xylitol, but not erythritol, increased rCBF in the hypothalamus, whereas glucose had the opposite effect; (ii) graph analysis of resting functional connectivity revealed a complex pattern of similarities and differences in brain network properties following xylitol, erythritol, and glucose; (iii) erythritol and xylitol induced a rise in CCK and PYY, (iv) erythritol had no and xylitol only minimal effects on glucose and insulin., Conclusion: Xylitol and erythritol have a unique combination of properties: no calories, virtually no effect on glucose and insulin while promoting the release of gut hormones, and impacting appetite-regulating neurocircuitry consisting of both similarities and differences with glucose.

Background & Aims: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe., Methods: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality., Results: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization., Conclusions: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The impact of oral erythritol on subsequent energy intake is unknown. The aim was to assess the effect of oral erythritol compared to sucrose, sucralose, or tap water on energy intake during a subsequent ad libitum test meal and to examine the release of cholecystokinin (CCK) in response to these substances. In this randomized, crossover trial, 20 healthy volunteers received 50 g erythritol, 33.5 g sucrose, or 0.0558 g sucralose dissolved in tap water, or tap water as an oral preload in four different sessions. Fifteen minutes later, a test meal was served and energy intake was assessed. At set time points, blood samples were collected to quantify CCK concentrations. The energy intake (ad libitum test meal) was significantly lower after erythritol compared to sucrose, sucralose, or tap water (p < 0.05). Before the start of the ad libitum test meal, erythritol led to a significant increase in CCK compared to sucrose, sucralose, or tap water (p < 0.001). Oral erythritol given alone induced the release of CCK before the start of the ad libitum test meal and reduced subsequent energy intake compared to sucrose, sucralose, or tap water. These properties make erythritol a useful sugar alternative.

The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591., (© 2022. The Author(s).)

Background: Glucose induces the release of gastrointestinal (GI) satiation hormones, such as glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY), in part via the activation of the gut sweet taste receptor (T1R2/T1R3)., Objectives: The primary objective was to investigate the importance of T1R2/T1R3 for the release of cholecystokinin (CCK), GLP-1, and PYY in response to D-allulose and erythritol by assessing the effect of the T1R2/T1R3 antagonist lactisole on these responses and as secondary objectives to study the effect of the T1R2/T1R3 blockade on gastric emptying, appetite-related sensations, and GI symptoms., Methods: In this randomized, controlled, double-blind, crossover study, 18 participants (5 men) with a mean ± SD BMI (in kg/m2) of 21.9 ± 1.7 and aged 24 ± 4 y received an intragastric administration of 25 g D-allulose, 50 g erythritol, or tap water, with or without 450 parts per million (ppm) lactisole, respectively, in 6 different sessions. 13C-sodium acetate was added to all solutions to determine gastric emptying. At fixed time intervals, blood and breath samples were collected, and appetite-related sensations and GI symptoms were assessed. Data were analyzed with linear mixed-model analysis., Results: D-allulose and erythritol induced a significant release of CCK, GLP-1, and PYY compared with tap water (all PHolm < 0.0001, dz >1). Lactisole did not affect the D-allulose- and erythritol-induced release of CCK, GLP-1, and PYY (all PHolm > 0.1). Erythritol significantly delayed gastric emptying, increased fullness, and decreased prospective food consumption compared with tap water (PHolm = 0.0002, dz = -1.05; PHolm = 0.0190, dz = 0.69; and PHolm = 0.0442, dz = -0.62, respectively)., Conclusions: D-allulose and erythritol stimulate the secretion of GI satiation hormones in humans. Lactisole had no effect on CCK, GLP-1, and PYY release, indicating that D-allulose- and erythritol-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

In patients with obesity, accelerated nutrients absorption is observed. Xylitol and erythritol are of interest as alternative sweeteners, and it has been shown in rodent models that their acute ingestion reduces intestinal glucose absorption. This study aims to investigate whether a chronic intake of xylitol and erythritol impacts glucose absorption in humans with obesity. Forty-six participants were randomized to take either 8 g of xylitol or 12 g of erythritol three times a day for five to seven weeks, or to be part of the control group (no substance). Before and after the intervention, intestinal glucose absorption was assessed during an oral glucose tolerance test with 3- Ortho -methyl-glucose (3-OMG). The effect of xylitol or erythritol intake on the area under the curve for 3-OMG concentration was not significant. Neither the time (pre or post intervention), nor the group (control, xylitol, or erythritol), nor the time-by-group interaction effects were significant ( p = 0.829, p = 0.821, and p = 0.572, respectively). Therefore, our results show that a chronic intake of the natural sweeteners xylitol and erythritol does not affect intestinal glucose absorption in humans with obesity.

Aim: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol., Materials and Methods: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples ( 13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated., Results: We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting., Conclusions: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

Background: Currently, the two most common bariatric procedures are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Long-term data comparing the two interventions in terms of their effect on body composition and bone mass density (BMD) are scarce., Objective: The aim of this study was to assess body composition and BMD at least 5 years after LSG and LRYGB., Setting: Department of Endocrinology and Nutrition, St. Claraspital Basel and St. Clara Research Ltd., Basel, Switzerland., Methods: Bariatric patients at least 5 years after surgery (LSG or LRYGB) were recruited, and body composition and BMD were measured by means of dual-energy X-ray absorptiometry. Data from body composition before surgery were included in the analysis. Blood samples were taken for determination of plasma calcium, parathyroid hormone, vitamin D3, alkaline phosphatase, and C-terminal telopeptide, and the individual risk for osteoporotic fracture assessed by the Fracture Risk Assessment Tool score was calculated. After surgery, all patients received multivitamins, vitamin D3, and zinc. In addition, LRYGB patients were prescribed calcium., Results: A total of 142 patients were included, 72 LSG and 70 LRYGB, before surgery: median body mass index 43.1, median age 45.5 years, 62.7% females. Follow-up after a median of 6.7 years. For LRYGB, the percentage total weight loss at follow-up was 26.3% and for LSG 24.1% (p = 0.243). LRYGB led to a slightly lower fat percentage in body composition. At follow-up, 45% of both groups had a T score at the femoral neck below -1, indicating osteopenia. No clinically relevant difference in BMD was found between the groups., Conclusions: At 6.7 years after surgery, no difference in body composition and BMD between LRYGB and LSG was found. Deficiencies and bone loss remain an issue after both interventions and should be monitored., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Objective: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care., Design: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed., Results: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%)., Conclusion: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness., Competing Interests: Competing interests: JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly, Allergan and Diasorin. OPN has received a research grant from Allergan. JM-I has served as a consultant for Casen Recordati and has received retribution from Allergan for formative actions. MC-F has received retribution from Allergan for formative actions. PB has served as speaker, consultant and advisory member for or has received research funding from Almirall, Allergan and Reckitt Benckiser. APA has received retribution from Allergan and Mylan for formative actions. DSB has served as lecturer for Astellas, AstraZeneca, KRKA and Abbott., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bariatric surgery is an effective therapeutic procedure for morbidly obese patients. The 2 most common interventions are sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB)., Objectives: The aim of this study was to compare microbiome long-term microbiome after SG and LRYGB surgery in obese patients., Setting: University Hospital, France; University Hospital, United States; and University Hospital, Switzerland., Methods: Eighty-nine and 108 patients who underwent SG and LRYGB, respectively, were recruited. Stools were collected before and 6 months after surgery. Microbial DNA was analyzed with shotgun metagenomic sequencing (SOLiD 5500 xl Wildfire). MSPminer, a novel innovative tool to characterize new in silico biological entities, was used to identify 715 Metagenomic Species Pan-genome. One hundred forty-eight functional modules were analyzed using GOmixer and KEGG database., Results: Both interventions resulted in a similar increase of Shannon's diversity index and gene richness of gut microbiota, in parallel with weight loss, but the changes of microbial composition were different. LRYGB led to higher relative abundance of aero-tolerant bacteria, such as Escherichia coli and buccal species, such as Streptococcus and Veillonella spp. In contrast, anaerobes, such as Clostridium, were more abundant after SG, suggesting better conservation of anaerobic conditions in the gut. Enrichment of Akkermansia muciniphila was also observed after both surgeries. Function-level changes included higher potential for bacterial use of supplements, such as vitamin B12, B1, and iron upon LRYGB., Conclusion: Microbiota changes after bariatric surgery depend on the nature of the intervention. LRYGB induces greater taxonomic and functional changes in gut microbiota than SG. Possible long-term health consequences of these alterations remain to be established., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Various studies from the past years examine the changing conditions and challenges in the veterinary sector. Secured access to public and private care services is a prerequisite for a holistically oriented health care system ("One Health"). In the present study, a multidimensional concept of accessibility to care services was used for the first time to determine and visualize the density of the animal health care system in Switzerland. Traditional indicators used to describe care structures focus either on availability or accessibility. In order to overcome the limitations of traditional indicators, the family of methods known as Floating-Catchment-Area-Methods (FCA) has been developed in care geographical research. The strength of FCA methods lies in the fact that they output accessibility independent of administrative boundaries and at the same time consider the spatial distance and available capacities. The study provides insight into the density of animal health care services using FCA methods and geographical information systems (GIS). Data on providers of veterinary services in the companion animal sector and, on the demand side, data on dogs and cats kept in Switzerland served as illustrative example. The result was interactive maps of the density of health care and the structure of spatial accessibility to veterinary providers and consumers. As expected, high spatial accessibility is found in the urban centers and the agglomerations of the Central Plateau. In contrast, spatial accessibility to medical services for dogs and cats is often lower in peripheral areas. Due to hitherto unavailable data, various analyses had to be postponed for the time being. For example, the model could of course be extended to all animal species and all types of medical services. In addition, it would also be possible to forecast the future density of health care, or to optimize the care system. Together with the relevant industry stakeholders, these gaps could be closed, and the model and the resulting findings could be further differentiated. The results should serve private actors in the concerned value chains, but also decision-makers in the public veterinary service, governmental authorities, agricultural bodies, universities, etc. as a basis for strategic decisions regarding the issue of medical supply density and care services in the animal sector.

Xylitol and erythritol are widely used in a variety of food and oral care products as sugar substitutes. Although a number of studies have been conducted on the health benefits of xylitol since the 1960s, erythritol only attracted the attention of researchers during the early 1990s. Historically, researchers mainly focused on the effects of xylitol and other sugar alcohols on oral and dental healthcare while the anti-diabetic or antihyperglycemic effects have only been revealed recently. Though a few reviews have been published on the health benefits of sugar alcohols in the last few decades, none of them closely evaluated the antihyperglycemic potential and underlying mechanisms, particularly with a focus on xylitol and erythritol. The current review thoroughly analyzes the anti-diabetic and antihyperglycemic effects as well as other metabolic effects of xylitol and erythritol using articles published in PubMed since the 1960s, containing research done on experimental animals and humans. This review will help researchers ascertain the controversies surrounding sugar alcohols, investigate further beneficial effects of them as well as aid food industries in exploring the possibilities of using sugar alcohols as anti-diabetic supplements in diabetic foods and food products.

Background: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear., Objective: To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG., Setting: University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland., Methods: Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery., Results: Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0-60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0-10 min), second-phase insulin secretion (AUC 10-60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change., Conclusion: Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Morbid obesity is a worldwide epidemic and is increasingly treated by bariatric surgery. Fatty liver is a common finding; almost half of all patients with non-alcoholic steatohepatitis develop steatohepatitis. Bariatric surgery improves steatohepatitis documented by liver biopsy and single voxel magnetic resonance imaging (MRI) techniques., Objective: To investigate changes before and after bariatric surgery using whole organ MRI quantification of liver, visceral, and subcutaneous fat., Setting: University of Basel Hospital and St. Clara Research Ltd, Basel, Switzerland., Methods: Sixteen morbidly obese patients were evaluated by abdominal MRI-scanning before and 3, 6, 12, and 24 months after bariatric surgery to measure percentage liver fat (%-LF), total liver volume (TLV) and visceral and subcutaneous adipose tissues (VAT and SAT). Fasting plasma samples were taken for measurement of glucose, insulin, blood lipids, and liver biomarkers. In a control group of 12 healthy lean volunteers, the liver biomarker was also measured., Results: The reproducibility of fat quantification by use of MRI was excellent. LF decreased significantly faster than VAT and SAT (%-LF vs. VAT p < 0.001 and %-LF vs. SAT p < 0.001). At certain time points, %-LF, VAT, and SAT were associated with changes in blood lipids and insulin., Conclusions: MRI quantification offers excellently reproducible results in measurement of liver fat and visceral and subcutaneous adipose tissues. Liver fat decreased significantly faster than visceral or subcutaneous adipose tissue. Decrease in %-LF and VAT is associated with decrease in total cholesterol, LDL, and plasma insulin.

Aims: Peripheral infusion of glucagon-like peptide-1 (GLP-1) can affect brain activity in areas involved in the regulation of appetite, including hypothalamic and reward-related brain regions. In contrast, the physiological role of endogenous GLP-1 in the central regulation of appetite has hardly been investigated., Materials and Methods: This was a randomized, cross-over trial that involved 12 healthy volunteers who received an intragastric (ig) glucose (gluc) load, with or without intravenous (iv) exendin9-39 (ex9-39; specific GLP-1 receptor antagonist). Functional magnetic resonance imaging was used to investigate the effect of endogenous GLP-1 on resting state functional connectivity (rsFC) between homeostatic and reward-related brain regions. Visual analogue scales were used to rate appetite-related sensations. Blood samples were collected for GI hormone measurements., Results: Administration of iv-ex9-39/ig-gluc induced a significantly higher rsFC, relative to ig-gluc administration, between the hypothalamus and the left lateral orbitofrontal cortex (OFC) as well as the left amygdala (P ≤ .001, respectively). Administration of iv-ex9-39/ig-gluc induced a significantly higher rsFC, relative to ig-gluc administration, between the right nucleus accumbens and the right lateral OFC (P < .001). Administration of iv-ex9-39/ig-gluc induced a significantly lower rsFC, relative to ig-gluc administration, between the midbrain and the right caudate nucleus (P = .001). Administration of ig-gluc significantly decreased prospective food consumption and increased sensations of fullness compared to pre-infusion baseline (P = .028 and P = .019, respectively); these effects were not present in the iv-ex9-39/ig-gluc condition., Conclusions: This pilot trial provides preliminary experimental evidence that glucose-induced endogenous GLP-1 affects central regulation of appetite by modulating rsFC in homeostatic and reward-related brain regions in healthy lean male participants in a GLP-1 receptor-mediated fashion., (© 2018 John Wiley & Sons Ltd.)

Background: Despite the increasing use of bariatric surgery as the most effective treatment of morbid obesity, there is still no consensus on its preoperative diagnostic workup. The aim of this study was to identify the pathologies of the endoscopic and radiologic investigations before performing bariatric surgery and to evaluate their impact on the patient management., Methods: Retrospective analysis of prospectively collected data of 1225 consecutive patients who underwent laparoscopic Roux-en-Y gastric bypass (n = 834) or sleeve gastrectomy (n = 391) at our institution. An abdominal ultrasound was performed in 1188 patients, 1190 patients underwent upper gastrointestinal (GI) endoscopy, 1178 patients underwent upper GI series, and 610 patients underwent esophageal manometry., Setting: Private hospital, Switzerland., Results: Gallstones were detected in 222 (21.0%) patients, and a synchronous cholecystectomy was performed in 220 (18.0%) patients. The upper GI series indicated hiatal hernias in 325 (27.6%) patients. The most common findings of the upper GI endoscopy were type-C gastritis (224 patients, 18.8%), reflux esophagitis (229 patients, 19.2%), Helicobacter pylori-positive gastritis (158, 13.3%), and hiatal hernia (55 patients, 4.6%). Additionally, we detected 1 Barrett's high-grade dysplasia, 2 Barrett's carcinomas, and 1 stomach cancer in asymptomatic patients, who were scheduled to have a sleeve gastrectomy. Esophageal motility disorders were detected in 104 (17.0%) individuals, who underwent esophageal manometry., Conclusions: We recommend performing abdominal sonography and upper GI endoscopy before bariatric surgery as they reveal findings, which influence the therapeutic approach. Upper GI series and esophageal manometry help to define patients not suitable for sleeve gastrectomy., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

The present randomized double-blinded cross-over study aims to extensively study the neural correlates underpinning cognitive functions in healthy subjects after acute glucose and fructose administration, using an integrative multimodal neuroimaging approach. Five minutes after glucose, fructose, or placebo administration through a nasogastric tube, 12 participants underwent 3 complementary neuroimaging techniques: 2 task-based functional magnetic resonance imaging (fMRI) sequences to assess working memory (N-back) and response inhibition (Go/No-Go) and one resting state fMRI sequence to address the cognition-related fronto-parietal network (FPN) and salience network (SN). During working memory processing, glucose intake decreased activation in the anterior cingulate cortex (ACC) relative to placebo, while fructose decreased activation in the ACC and sensory cortex relative to placebo and glucose. During response inhibition, glucose and fructose decreased activation in the ACC, insula and visual cortex relative to placebo. Resting state fMRI indicated increased global connectivity strength of the FPN and the SN during glucose and fructose intake. The results demonstrate that glucose and fructose lead to partially different partially overlapping changes in regional brain activities that underpin cognitive performance in different tasks.

Background: Many patients with moderate to severe Crohn's disease (CD) are treated with infliximab (IFX). As most of these patients experience a long-lasting therapy, the outcome and withdrawal of IFX treatment are important clinical questions., Methods: In this retrospective study, we analyzed the treatment outcome in moderate to severe CD patients with a steroid-dependent/refractory disease course started on IFX. Withdrawal of IFX was evaluated in patients with deep remission defined as clinical (Harvey-Bradshaw Index ≤4), biochemical (fecal calprotectin [FC] ≤150 μg/g stool) over a period of 2 years, and endoscopic and histological remission before discontinuation of IFX., Results: After induction with IFX, clinical remission was observed in 45/109 patients (41.3%) and clinical response in 61/109 patients (56.0%). Only 8/109 patients (7.3%) achieved deep remission and therefore could be discontinued from IFX therapy. In 4 of these patients (50%), relapse was observed after discontinuation of IFX treatment. FC decreased in these 8 patients in deep remission from 652 ± 168 μg/g stool (mean ± SE) at baseline to 24.9 ± 8.1 μg/g stool at 14 weeks. When compared to patients in deep remission, FC had decreased significantly less at 14 weeks in patients in clinical remission after induction with IFX ( n = 31; 154 ± 55 μg/g stool; p = 0.01), in patients with clinical response after induction achieving clinical remission during the maintenance phase ( n = 11; 352 ± 67 μg/g stool; p = 0.004), or in patients with chronic active disease course on maintenance therapy ( n = 50; 645 ± 93 μg/g stool; p < 0.001)., Conclusion: A low discontinuation rate was observed for steroid-dependent/refractory moderate to severe CD patients with IFX treatment. As FC showed a more or less pronounced decrease depending on the response to the IFX treatment, monitoring of FC may become a noninvasive tool for tailoring biological therapy in CD patients.

Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown., Objective: To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events., Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period., Interventions: Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110)., Main Outcomes and Measures: The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events., Results: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass., Conclusions and Relevance: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery., Trial Registration: clinicaltrials.gov Identifier: NCT00356213.

Extracellular vesicle (EV) production is a universal feature of metazoan cells as well as prokaryotes (bMVs - bacterial microvesicles). They are small vesicles with phospholipid membrane carrying proteins, DNA and different classes of RNAs and are heavily involved in intercellular communication acting as vectors of information to target cells. For the last decade, the interest in EV research has exponentially increased though thorough studies of their roles in various pathologies that was not previously possible due to technical limitations. This review focuses on research evaluating the role of EV production in gastrointestinal (GI) cancer development in conjunction with GI microbiota and inflammatory diseases. We also discuss recent studies on the promising role of EVs and their content as biomarkers for early diagnosis of GI cancers. The bMVs have also been implicated in the pathogenesis of GI chronic inflammatory diseases, however, possible role of bMVs in tumorigenesis remains underestimated. We propose that EVs from eukaryotic cells as well as from different microbial, fungi, parasitic species and edible plants in GI tract act as mediators of intracellular and inter-species communication, particularly facilitating tumor cell survival and multi-drug resistance. In conclusion, we suggest that matching sequences from EV proteomes (available from public databases) with known protein sequences of microbiome gut bacteria will be useful in identification of antigen mimicry between evolutionary conservative protein sequences. Using this approach we identified Bacteroides spp. pseudokinase with activation loop and homology to PDGFRα, providing a proof-of-concept strategy. We speculate that existence of microbial pseudokinase that 'mimics' PDGFRα may be related to PDGFRα and Bacteroides spp. roles in colorectal carcinogenesis that require further investigation., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain., Purpose: To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans., Methods: We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement., Outcome: We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9)., Conclusions: The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact., (Copyright © 2017. Published by Elsevier GmbH.)

The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na + /glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.

The effects of altered gastric emptying on glucose absorption and kinetics are not well understood in nondiabetic obese adults. The aim of this work was to develop a physiology-based model that can characterize and compare interactions among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese and lean healthy adults. Dynamic glucose, insulin, and gastric emptying (measured with breath test) data from 12 nondiabetic obese and 12 lean healthy adults were available until 180 min after an oral glucose tolerance test (OGTT) with 10, 25, and 75 g of glucose. A physiology-based model was developed to characterize glucose kinetics applying nonlinear mixed-effects modeling with NONMEM7.3. Glucose kinetics after OGTT was described by a one-compartment model with an effect compartment to describe delayed insulin effects on glucose clearance. After the interactions between individual gastric emptying and glucose absorption profiles were accounted for, the glucose absorption rate was found to be similar in nondiabetic obese and lean controls. Baseline glucose concentration was estimated to be only marginally higher in nondiabetic obese subjects (4.9 vs. 5.2 mmol/l), whereas insulin-dependent glucose clearance in nondiabetic obese subjects was found to be cut in half compared with lean controls (0.052 vs. 0.029 l/min) and the insulin concentration associated with 50% of insulin-dependent glucose elimination rate was approximately twofold higher in nondiabetic obese subjects compared with lean controls (7.1 vs. 15.3 μU/ml). Physiology-based models can characterize and compare the dynamic interaction among gastric emptying, glucose absorption and glycemic control in populations of interest such as lean healthy and nondiabetic obese adults., (Copyright © 2017 the American Physiological Society.)

Objective: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS)., Methods: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ± 11 kg/m, mean age was 43 ± 5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications., Results: Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ± 21.9% vs. 76.6 ± 20.9%, P = 0.139; 2 years: 74.7 ± 29.8% vs. 77.7 ± 30%, P = 0.513; 3 years: 70.9 ± 23.8% vs. 73.8 ± 23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively., Conclusions: In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB., Competing Interests: The authors report no conflicts of interest.

The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials., (Copyright © 2017 the American Physiological Society.)

Background/objectives: Gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance satiation peptide secretion could provide a therapeutic approach for obesity. Carbohydrates and lipids have been extensively investigated in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion., Participants/methods: The study was conducted as a randomized (balanced), double-blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese participants were included. Participants received intragastric loads of L-trp (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g glucose and 300 mL tap water served as control treatments., Results: Results of the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018), and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii) neither of the amino acids modulated subjective appetite feelings; and iv) the two amino acids did not alter insulin or glucose concentrations., Conclusions: L-trp is a luminal regulator of CCK release with effects on gastric emptying, an effect that could be mediated by CCK. L-trp's effect on GLP-1 secretion is only minor. At the doses given, the two amino acids did not affect subjective appetite feelings., Trial Registration: ClinicalTrials.gov NCT02563847., Competing Interests: The authors have declared that no competing interests exist.

Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation.

Purpose: A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy., Experimental Design: A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) ≥1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I-II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers., Results: The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively., Conclusions: We report the validation of a novel blood test, Colox®, for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy. Clin Cancer Res; 22(18); 4604-11. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: After laparoscopic Roux-en-Y gastric bypass (LRYGB), many patients suffer from dumping syndrome. Oral glucose tolerance tests are usually carried out with 50-75 g of glucose. The aim of this study was to examine whether minimal glucose loads of 10 g and 25 g induce a reliable secretion of satiation peptides without dumping symptoms after LRYGB. In addition, lean and obese controls were examined., Objective: The objective of this study was to determine the effects of low oral glucose loads on incretin release and gastric emptying., Setting: All surgical procedures were performed by the same surgeon (RP) at the St. Claraspital Basel in Switzerland. Oral glucose challenges were carried out at the University Hospital of Basel (Phase 1 Research Unit)., Methods: Eight patients 10±.4 weeks after LRYGB (PostOP; body mass index [BMI]: 38.6 kg/m 2 ±1.7) as well as 12 lean controls (LC; BMI: 21.8 kg/m 2 ±.6) and 12 obese controls (OC; BMI 38.7 kg/m 2 ±1.3) received 10 g and 25 g of oral glucose. We examined clinical signs of dumping syndrome; plasma glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, and peptide tyrosine tyrosine concentrations; and gastric emptying with a 13 C-sodium acetate breath test., Results: No signs of dumping were seen in PostOP. Compared with OC, LC showed lower fasting glucose, insulin, and C-peptide, and lower homeostasis model assessment (HOMA) and AUC-180 for insulin and C-peptide. In PostOP, fasting insulin, HOMA and AUC-180 for insulin was lower and no difference was found in fasting C-peptide or AUC-180 for C-peptide compared to OC. There was no significant difference in fasting glucose, insulin, C-peptide, HOMA and AUC-180 for insulin in PostOP compared to LC, but AUC-180 for C-peptide was higher in PostOP. AUC-60 for gut hormones was similar in OC and LC and higher in PostOP compared to OC or LC. gastric emptying was slower in LC and OC compared with PostOP., Conclusion: After LRYGB, 25 g oral glucose is well tolerated and leads to reliable secretion of gut hormones. Fasting glucose, insulin and C-peptide are normalized, while glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine are overcorrected. Pouch emptying is accelerated after LRYGB., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies. Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are released from the gut in response to food intake, promote satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers were given 75 g of glucose, 50 g of xylitol, or 75 g of erythritol in 300 ml of water or placebo (water) by a nasogastric tube. We examined plasma glucose, insulin, active GLP-1, CCK, and GE with a [(13)C]sodium acetate breath test and assessed subjective feelings of satiation. Xylitol and erythritol led to a marked increase in CCK and GLP-1, whereas insulin and plasma glucose were not (erythritol) or only slightly (xylitol) affected. Both xylitol and erythritol induced a significant retardation in GE. Subjective feelings of appetite were not significantly different after carbohydrate intake compared with placebo. In conclusion, acute ingestion of erythritol and xylitol stimulates gut hormone release and slows down gastric emptying, whereas there is no or only little effect on insulin release., (Copyright © 2016 the American Physiological Society.)

Background/objectives: The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads., Subjects/methods: The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water., Results: Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects., Conclusions: It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance., Trial Registration: ClinicalTrials.gov NCT01875575.

Background and Study Aims: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware., Patients and Methods: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists’ knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies)., Results: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 – 5.5 minutes) without intervention and 6 minutes (IQR 4 – 9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 – 9 minutes) and 8 minutes (IQR 7 – 11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 – 8.705; P < 0.001)., Conclusions: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR.

In response to luminal food stimuli during meals, enteroendocrine cells release gastrointestinal (GI) peptides that have long been known to control secretory and motor functions of the gut, pancreas and liver. Glucagon-like peptide-1 (GLP-1) has emerged as one of the most important GI peptides because of a combination of functions not previously ascribed to any other molecule. GLP-1 potentiates glucose-induced insulin secretion, suppresses glucagon release, slows gastric emptying and may serve as a satiation signal, although the physiological status of the latter function has not been fully established yet. Here we review the available evidence for intestinal GLP-1 to fulfill a number of established empirical criteria for assessing whether a hormone inhibits eating by eliciting physiological satiation in man and rodents.

Background/aims: Taste perception is one of the most important primary oral reinforcers, driving nutrient and energy intake as well as toxin avoidance. Taste receptors in the gastrointestinal tract might as well impact appetitive or aversive behavior and thus influence learning tasks and a close relation of neural taste processing and working memory networks seems plausible., Methods: In the present pilot study, we determined the effects of five taste qualities "bitter" (quinine), "sweet" (glucose), "sour" (citric acid), "salty" (NaCl) and "umami" (monosodium glutamate, MSG) on working memory processing using functional MRI and their effect on plasma insulin and glucose levels. On six separate occasions, subjects received one of the following test substances dissolved in 200 mL tap water via a nasogastric tube (to circumvent the oral cavity): 1) 2g citric acid corresponding to 52 mM, 2) 2g NaCl; 171 mM, 3) 0.017g quinine; 0.26 mM, 4) 1g monosodium glutamate; 30 mM, 5) 25g glucose; 694 mM and 6) 200 mL tap water (placebo)., Results: The taste qualities "bitter" and "umami" significantly altered brain activation patterns in the primary gustatory cortex as well as in subcortical structures, previously reported to be involved in emotional learning and memory. In contrast, glucose did not reveal any statistically significant brain activation difference. Working memory performance was not different over the six treatments. Plasma insulin and glucose levels were not affected by the different taste substances (MSG, quinine, NaCl and citric acid)., Conclusions: in this pilot trial, we demonstrate that acute intragastric administration of different taste substances does not affect working memory performance in humans. However, "umami" and "bitter" have effects on brain areas involved in neural working memory, overpowering the effects of "sweet", "salty" and "sour" reception., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Gastric emptying (GE) is delayed in a subset of patients with inflammatory bowel disease (IBD). We have shown before that altered release of gastrointestinal hormones may contribute to GE disturbances, but overall effects of disease activity remain unclear. Thus, we aimed to evaluate GE in patients with IBD during active disease and following therapy., Design: A total of 20 healthy subjects (HC) and 26 patients with IBD hospitalized because of an acute episode of their disease (Crohn's disease (CD) n = 13, ulcerative colitis (UC) n = 13) underwent a standardized (13) C-octanoic acid GE breath test (baseline test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured periodically throughout the test. A total of 16 patients underwent a second GE test after 3-4 months of therapy., Results: At baseline, nine patients with IBD had pathologically delayed GE half-time (T½ > 150 min) (P = 0·028 vs. HC). Moreover, T½ was significantly longer in the total group of patients with IBD than in HC (129 ± 12 min vs. 96 ± 7, P = 0·030). Postprandial GLP-1 responses were elevated in IBD (P = 0·002 vs. HC) and correlated with T½ (P = 0·05). Following therapy clinical activity indices and T½ were decreased in IBD (P ≤ 0·01 vs. baseline), and T½ no longer differed from HC (P > 0·5). Moreover, GLP-1 plasma levels decreased significantly (P = 0·031)., Conclusions: Higher disease activity in IBD is associated with prolonged GE and increased release of GLP-1. Following effective therapy, GE is accelerated and GLP-1 release decreases significantly. Thus, increased release of GLP-1 from the inflamed mucosa might contribute to GE disturbances in IBD., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study aimed to characterise lean and obese phenotypes according to diet and body composition, and to compare fasting and postprandial appetite and metabolic profiles following a high-fat test meal. A total of ten lean (BMI40 and 30 kg/m2) high-fat consumers (OHF; >40 % energy from fat) were recruited. Before and following the test meal (4727 kJ (1130 kcal), 77 % fat, 20 % carbohydrate (CHO) and 3 % protein), fasting plasma glucose, insulin, leptin, ghrelin, peptide YY (PYY), RER, RMR and subjective appetite ratings (AR) were measured for 6 h. Thereafter, subjects consumed a self-selected portion of a standardised post-test meal (40 % fat, 45 % CHO and 15 % protein) and reported AR. Fasting (P=0·01) and postprandial (P<0·001) fat oxidation was significantly higher in LHF than in LLF but was not different between LHF and OHF. Although similar between the lean groups, fasting and postprandial energy expenditures were significantly higher in OHF compared with LHF (P<0·01). Despite similar AR across groups, LLF consumed a relatively greater quantity of the post-test meal than did LHF (7·87 (sd 2·96) v. 7·23 (sd 2·67) g/kg, P=0·013). The lean groups showed appropriate changes in plasma ghrelin and PYY following the test meal, whereas the OHF group showed a blunted response. In conclusion, the LHF phenotype had a greater capacity for fat oxidation, which may be protective against weight gain. OHF individuals had a blunted appetite hormone response to the high-fat test meal, which may subsequently increase energy intake, driving further weight gain.

Background & Aims: Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD., Methods: Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters., Results: In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019)., Conclusions: In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24 hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.

Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones. Recent studies have begun to elucidate brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging (MRI), but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear. In this paper, we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system. Using a cross-over, double-blind, placebo-controlled design, we compared resting state functional connectivity (rsFC) strengths within the basal ganglia/limbic network in 12 healthy lean males. Each subject was administered fructose, glucose and placebo on three separate occasions. Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite. Glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, glucose increased rsFC of the left caudatus and putamen, precuneus and lingual gyrus more than fructose, whereas within the basal ganglia/limbic network, fructose increased rsFC of the left amygdala, left hippocampus, right parahippocampus, orbitofrontal cortex and precentral gyrus more than glucose. Moreover, compared to fructose, the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin. Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network, which are probably mediated by different insulin levels. A larger study would be recommended in order to confirm these findings.

Background: Non-invasive monitoring of inflammatory bowel disease is an unmet clinical need as patients in clinical remission may have residual mucosal inflammation preceding clinical relapse., Aims: We aimed to assess the value of fecal calprotectin and standardized clinical activity scoring to monitor disease activity in ulcerative colitis under medical treatment., Methods: Forty-one patients with ulcerative colitis were included in a prospective observational study. Medical treatment was guided by clinical judgement of treating physicians. Fecal calprotectin and the clinical activity index (CAI) were measured blinded to treating physicians every 2 months until the end of follow-up. Twenty-six patients received colonoscopy for clinical reason., Results: As defined by the CAI, patients were in clinical remission (63.4 %), having mild (26.8 %) or moderate (11.2 %) disease activity. Of those in clinical remission (CAI ≤ 4), 86.4 % showed residual endoscopic activity (Mayo Score ≥1). Calprotectin levels were higher in endoscopically active disease (779.0 vs 331.5 μg/g, P = 0.034) and calprotectin testing identified more patients with endoscopic disease activity (86.4 %) than the CAI (45.5 %, P = 0.034). Medical treatment was escalated in 90.2 % during the study. Values of the CAI and calprotectin correlated with therapy escalation (OR 3.94 and 3.22, respectively). Only for calprotectin, changes between two measurements were related to intensified medical treatment (OR 1.39)., Conclusion: Fecal calprotectin was similarly useful to the CAI to monitor disease activity of ulcerative colitis during medical treatment but identified endoscopic disease activity far more reliably. Changes of calprotectin values between measurements might indicate clinical relapse earlier than the CAI.