Disaccharidase deficiencies and gastrointestinal symptoms in patients referred to gastroscopic examination: a single center study from Norway.

OBJECTIVE: Gastrointestinal illnesses have been reported in relation to low disaccharidase activity, yet both the prevalence of disaccharidase deficiency and its association with gastrointestinal symptoms and irritable bowel syndrome (IBS) are largely unknown. We aimed to determine the association between low activity of disaccharidase enzymes on gastrointestinal symptoms and presence of IBS. METHODS: Patients referred for gastroscopic examination due to gastrointestinal complaints were consecutively included. A pinch biopsy was taken from the distal part of duodenum, and disaccharidase activity was measured using the Dahlqvist method. Gastrointestinal symptom severity was measured using IBS-Symptom Severity Score (IBS-SSS). RESULTS: A total of 40 patients were included. Disaccharidase deficiency was detected in 24 patients (60%). Half of the patients (n = 21) had IBS according to Rome IV criteria. A majority (75%) of all patients reported moderate to severe gastrointestinal symptoms. Moderate to severe gastrointestinal symptoms were reported by 16 patients (67%) with disaccharidase deficiency and in 14 patients (88%) with normal disaccharidase activity. Lactase deficiency was detected in 22 patients (55%), maltase deficiency in 11 patients (28%), sucrase deficiency in 9 patients (23%), isomaltase deficiency in 13 patients (33%) and glucoamylase deficiency in 12 patients (30%). The activity of all enzymes was reduced in 8 patients (20%). Degree of disaccharidase deficiency was not associated with either the severity of gastrointestinal symptoms or the diagnosis of IBS. Enzymes levels were not associated with gastrointestinal symptom scores. CONCLUSION: Our findings did not reveal any association between biochemically measured disaccharidase deficiency and gastrointestinal symptoms or the presence of IBS.

Diagnosing sucrase-isomaltase deficiency: a comparison of a 13C-sucrose breath test and a duodenal enzyme assay.

BACKGROUND: Reduced activity of the sucrase-isomaltase (SI) enzyme can cause gastrointestinal symptoms. Biochemical measurement of SI activity in small intestinal biopsies is presently considered the gold standard for the diagnosis of SI deficiency, but this invasive test is not suitable as a routine diagnostic tool. AIM: To evaluate a 13C-sucrose-breath test (13CSBT) as a diagnostic tool for SI deficiency in an adult population. METHODS: 13CSBT results were compared to sucrase activity measured in duodenal biopsies. RESULTS: Forty patients with gastrointestinal symptoms were included in the study, 4 of whom had celiac disease and the rest (n = 36) had normal histological findings. Nine patients (22.5%) had low sucrase activity measured using duodenal biopsies. No correlation was observed between enzymatic sucrase activity and the 13CSBT results. The 13CSBT-curves for the celiac patients versus patients with normal duodenal histology demonstrated that the patients with celiac disease were within the lower range of the distribution. CONCLUSION: We observed a mismatch between the 13CSBT results and the biochemically measured sucrase activity, suggesting that SI activity is not uniformly distributed throughout the small intestines. This methodological discrepancy should be acknowledged when diagnosing SI deficiency.

Diet-microbiota interaction in irritable bowel syndrome: looking beyond the low-FODMAP approach.

BACKGROUND: Diet is one of the main modulators of the gut microbiota, and dietary patterns are decisive for gut-microbiota-related diseases, including irritable bowel syndrome (IBS). The low-FODMAP diet (LFD) is commonly used to treat IBS, but its long-term effects on microbiota, symptoms and quality of life (QoL) are unclear. Alternative dietary strategies promoting beneficial gut microbiota, combined with reduced symptoms and improved QoL, are therefore of interest. AIMS: To review current evidence on the diet-microbiota-interaction as a modulator of IBS pathophysiology, and dietary management of IBS, with particular emphasis on strategies targeting the gut microbiota, beyond the LFD. METHODS: Literature was identified through PubMed-searches with relevant keywords. RESULTS: Dietary patterns with a low intake of processed foods and a high intake of plants, such as the Mediterranean diet, promote gut microbiota associated with beneficial health outcomes. In contrast, Western diets with a high intake of ultra-processed foods promote a microbiota associated with disease, including IBS. Increasing evidence points towards dietary strategies consistent with the Mediterranean diet being equal to the LFD in alleviating IBS-symptoms and having a less negative impact on QoL. Timing of food intake is suggested as a gut microbiota modulator, but little is known about its effects on IBS. CONCLUSIONS: Dietary recommendations in IBS should aim to target the gut microbiota by focusing on improved dietary quality, considering the impact on both IBS-symptoms and QoL. Increased intake of whole foods combined with a regular meal pattern and limitation of ultra-processed foods can be beneficial strategies beyond the LFD.

Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: recent developments and future perspectives

Increased knowledge regarding the implications of gut microbiota in irritable bowel syndrome (IBS) suggests that a disturbed intestinal microenvironment (dysbiosis) might promote the development and maintenance of IBS symptoms and affects several pathways in the pathology of this multifactorial disease. Accordingly, manipulation of the gut microbiota in order to improve IBS symptoms has evolved as a novel treatment strategy in the last decade. Several different approaches have been investigated in order to improve the gut microbiota composition. Dietary modifications including supplementation with fibers, prebiotics, and probiotics are shown to improve symptoms and composition of gut microbiota in IBS; however, the exact probiotic mixture beneficial for each individual remains to be identified. The use of antibiotics still needs confirmation, although promising results have been reported with use of rifaximin. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and several placebo-controlled trials investigating FMT obtain promising results regarding symptom reduction and gut microbiota manipulation in IBS. However, more data regarding long-term effects are needed before FMT can be integrated as a customized treatment for IBS in the clinical routine.

Non-coeliac gluten sensitivity and the spectrum of gluten-related disorders: an updated overview.

The spectrum of gluten-related disorders includes coeliac disease (CD), wheat allergy (WA) and the suggested entity of non-coeliac gluten sensitivity (NCGS). An increasing number of the world's population are avoiding gluten due to the assumption of health benefits and self-diagnosed gastrointestinal and/or extra-intestinal symptoms. Unlike CD and WA, NCGS is a relatively new entity with an unknown prevalence and mechanisms, complicated by recent literature suggesting that gluten is not the only food component that may trigger symptoms experienced by this group of patients. The term 'non-coeliac wheat sensitivity' has been proposed as a more accurate term, allowing inclusion of other non-gluten wheat components such as fructans and amylase-trypsin inhibitors. There is inconsistent evidence when evaluating the effects of a gluten challenge in patients with suspected NCGS and there is a need for a standardised procedure to confirm the diagnosis, ultimately enabling the optimisation of clinical care. The present review will give an overview of the different gluten-related disorders and discuss the most recent scientific evidence investigating NCGS.

Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet.

PURPOSE: Markers for gut integrity and inflammation have received increasing interest as intestinal permeability and innate immune system activation are suggested as possible pathophysiological mechanisms in non-celiac gluten sensitivity (NCGS). We aimed to assess relevant biomarkers in NCGS by analyzing serum levels of gut integrity and permeability markers, pro-inflammatory cytokines and antigliadin IgG in patients with suspected NCGS on a gluten-free diet (GFD), and compare them to serum levels in patients with irritable bowel syndrome (IBS) and healthy controls (HC). PATIENTS AND METHODS: Serum samples collected from patients with suspected NCGS on a GFD (n=20, 14 women, 21-62 years), IBS (n=20, 16 women, 24-67 years) and HC (n=20, 14 women, 21-54 years) were analyzed. IBS severity scoring system (IBS-SSS) was applied to evaluate gastrointestinal symptoms. RESULTS: The IBS-SSS score was higher in subjects with suspected NCGS and IBS patients compared to HC (p<0.0001). No significant differences were found in the serum levels of any of the gut integrity and permeability markers, cytokines or antigliadin IgG antibodies between the three groups. However, positive correlations were observed between claudin-1 and i-FABP, and between claudin-1 and antigliadin IgG antibodies. CONCLUSION: No differences in serum levels of gut integrity and permeability markers, pro-inflammatory cytokines or antigliadin IgG antibodies were found among patients with suspected NCGS on a GFD, IBS and HC.

Comparison of gut microbiota profile in celiac disease, non-celiac gluten sensitivity and irritable bowel syndrome: A systematic review.

Gut microbiota is vital for human health. Shifts in the microbial diversity can affect bacterial function, and dysbiosis is associated with a variety of gastrointestinal disorders, including celiac disease (CD) and irritable bowel syndrome (IBS). The distinction between IBS and non-celiac gluten sensitivity (NCGS) is unclear, and it is conceivable that the gut microbiota profile of these patients may overlap. To our knowledge, no existing literature has evaluated the microbial characteristics in CD, IBS, and NCGS. Hence, this systematic review aims to compare the gut microbiota profile in these three diagnoses. A literature search was conducted in PubMed (Medline) until April 2019. Studies investigating bacterial diversity in the gut of patients with CD, IBS, and NCGS were eligible. Inclusion criteria were observational studies and randomized controlled trials reporting bacterial profile at baseline. Ninety-one articles were identified, of which 13 trials were eligible for inclusion. Overall, the bacterial composition of the gut microbiota of patients with CD and those with IBS shared the many similarities. The microbial richness was correspondingly reduced in these patient-groups compared with healthy controls, but this was not reported for NCGS. Our findings suggest that the bacterial profiles of patients with IBS and CD share certain disease-specific trends. Fewer similarities were observed between the bacterial profiles of patients with IBS and NCGS. Notably, the data are limited; thus, no solid conclusions can be made on the basis of these findings alone. The suggested trends can be a valuable basis for further research.

Effects of Plant-Based Diets on Weight Status: A Systematic Review.

There is an increasing number of people who convert to a plant-based diet. The desire for health benefits, including weight management, is often a contributing factor behind this dietary choice. The purpose of this review was to evaluate intervention studies assessing the effects of different plant-based diets on body mass index and weight. A literature search was conducted in PubMed until December 2019. Twenty-two publications from 19 studies were included. The majority of them were randomized controlled trials comparing a low-fat vegan diet to an omnivore diet in participants with overweight, type 2 diabetes mellitus and/or cardiovascular disease. All studies reported weight reductions, of which seven revealed significant differences, and four revealed non-significant differences between the intervention and the control groups. The results suggest that plant-based diets may improve weight status in some patient groups. Due to restrictions in fat intake in many studies, followed by reduced energy intake, the effects of the different interventions differ depending on the specific plant-based diets investigated. Future research should aim to include a representative study population and apply study diets without dietary restrictions.

Effects of Plant-Based Diets on Outcomes Related to Glucose Metabolism: A Systematic Review.

According to the rising prevalence of obesity and metabolic disorders leading to impaired glucose metabolism, effective strategies to prevent and/or delay the onset of disease are of great need. A plant-based diet has been suggested as an effective lifestyle change that may reduce the degree of obesity and improve outcomes related to glucose metabolism. This systematic review aimed to evaluate the effect of a plant-based diet on outcomes related to glucose metabolism. A literature search was conducted in the database PubMed until January 30, 2020. Randomized controlled trials investigating the effect of a plant-based dietary intervention on outcomes related to glucose metabolism in human subjects compared to an omnivorous diet were eligible for inclusion. Of 65 publications identified, nine trials on subjects with overweight/obesity, type 2 diabetes mellitus, or cardiovascular disease were included. Five studies reported that the plant-based intervention significantly improved markers of glycemic control from baseline to end point, of which four revealed a significant improvement in the intervention group compared to the control intervention. The remaining four studies did not observe a significant effect of a plant-based intervention on outcomes related to glucose metabolism. Our findings suggest that a shift to a plant-based diet may lead to favorable effects on glycemic control in individuals diagnosed with type 2 diabetes mellitus and/or obesity. The data were however somewhat conflicting, and the included trials reported results based on different intervention diets and study populations. Overall, no clear conclusions regarding effects of different plant-based diets can be drawn based on the current findings alone.

The Effect of Supplementation with Low Doses of a Cod Protein Hydrolysate on Satiety Hormones and Inflammatory Biomarkers in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study.

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.

Fish-derived proteins and their potential to improve human health.

Emerging evidence from studies evaluating the effect of lean fish consumption in humans suggests that proteins from fish have several beneficial metabolic effects. Rest, or waste, material from the fishing industry contains high-quality proteins, and utilization of this material offers novel possibilities for the development of protein-containing products that might be beneficial for human consumption. Fish-derived peptides containing bioactive amino acid sequences suggested to beneficially influence pathways involved in body composition, hypertension, lipid profile, and regulation of glucose metabolism are of particular interest, although the results of published studies are conflicting. This review aims to summarize current knowledge from animal studies and clinical interventions in humans evaluating the effects of lean fish, fish proteins, and fish-derived peptides on outcomes related to metabolic health. Fish proteins have a high content of taurine, and animal trials suggest that taurine mediates some of the beneficial effects observed thus far, although the mechanisms by which fish peptides exert their action are not yet elucidated. At this time, the literature is inconsistent, and there is insufficient mechanistic evidence to support a beneficial effect of fish-derived peptides on metabolic health.

Probiotics in Irritable Bowel Syndrome: An Up-to-Date Systematic Review.

Irritable bowel syndrome (IBS) is a frequent functional gastrointestinal disorder, and alterations in the gut microbiota composition contributes to symptom generation. The exact mechanisms of probiotics in the human body are not fully understood, but probiotic supplements are thought to improve IBS symptoms through manipulation of the gut microbiota. The aim of this systematic review was to assess the latest randomized controlled trials (RCTs) evaluating the effect of probiotic supplementation on symptoms in IBS patients. A literature search was conducted in Medline (PubMed) until March 2019. RCTs published within the last five years evaluating effects of probiotic supplements on IBS symptoms were eligible. The search identified in total 35 studies, of which 11 met the inclusion criteria and were included in the systematic review. Seven studies (63.6%) reported that supplementation with probiotics in IBS patients significantly improved symptoms compared to placebo, whereas the remaining four studies (36.4%) did not report any significant improvement in symptoms after probiotic supplementation. Of note, three studies evaluated the effect of a mono-strain supplement, whereas the remaining eight trials used a multi-strain probiotic. Overall, the beneficial effects were more distinct in the trials using multi-strain supplements with an intervention of 8 weeks or more, suggesting that multi-strain probiotics supplemented over a period of time have the potential to improve IBS symptoms.

Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome.

Peptides from fish may beneficially affect several metabolic outcomes, including gut health and inflammation. The effect of fish peptides in subjects with irritable bowel syndrome (IBS) has not previously been investigated, hence this study aimed to evaluate the effect of a cod protein hydrolysate (CPH) supplement on symptom severity, gut integrity markers and fecal fermentation in IBS-patients. A double-blind, randomized parallel-intervention with six weeks of supplementation with 2.5 g CPH (n = 13) or placebo (n = 15) was conducted. The outcomes were evaluated at baseline and the end of the study. The primary outcomes were symptom severity evaluated by the IBS severity scoring system (IBS-SSS) and quality of life. The secondary outcomes included gut integrity markers and pro-inflammatory cytokines in serum, fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) and fecal calprotectin. The groups were comparable at baseline. The total IBS-SSS-scores were reduced in both the CPH-group (298 ± 69 to 236 ± 106, p = 0.081) and the placebo-group (295 ± 107 to 202 ± 103, p = 0.005), but the end of study-scores did not differ (p = 0.395). The concentrations of serum markers and SCFAs did not change for any of the groups. The baseline measures for the whole group showed that the total SCFA concentrations were inversely correlated with the total IBS-SSS-score (r = -0.527, p = 0.004). Our study showed that a low dose of CPH taken daily by IBS-patients for six weeks did not affect symptom severity, gut integrity markers or fecal fermentation when compared to the placebo group.

Erratum: Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2018.23.].

Acute effect of a cod protein hydrolysate on postprandial acylated ghrelin concentration and sensations associated with appetite in healthy subjects: a double-blind crossover trial.

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.

Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial.

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.