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.publishedVersio

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.publishedVersio

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.publishedVersio

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.publishedVersio

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.publishedVersio

Health effects of supplementation with cod protein hydrolysate: Impact on glucose metabolism and appetite in healthy subjects and gut health in irritable bowel syndrome

Background: Emerging evidence suggest that peptides from fish have several beneficial health effects in the human body. A huge part of the world’s population are affected by life-style diseases related to overweight and obesity, leading to impaired glucose metabolism and other adverse metabolic impairments. In addition, around one out of ten individuals are affected by irritable bowel syndrome (IBS), a diagnosis that most often is only partly controlled by dietary changes and/or pharmacological treatment and cause reduced quality of life. A dietary supplement contributing to increased utilization of residual material from the fishing industry, capable of improve health outcomes related to metabolism and gastrointestinal function, can arguably be regarded valuable both for those individuals affected as well as contribute to a more sustainable industry. Aim: To investigate the effects of a supplement with cod protein hydrolysate (CPH) on glucose metabolism and appetite in healthy subjects, and on gut health in patients with IBS. Method: Three randomized double-blinded clinical intervention studies were conducted. Study 1 was a crossover trial in 41 healthy, middle-aged to elderly adults, and included two study days, with 4-7 days wash out in between. The intervention consisted of 20 mg of CPH (or control) per kg body weight, given before a standardized breakfast meal. Study 2 was a dose-range study in 31 healthy, older subjects receiving four different doses of CPH equivalent to 10, 20, 30 or 40 mg/kg body weight in random order, each dose taken daily for one week, with a week of wash-out in between. Primary outcome in both studies was postprandial response in glucose metabolism, measured by samples of serum glucose, insulin and plasma glucagon-like peptide 1 (GLP-1) (Paper I and III), and secondary outcomes (Study 1) were postprandial acylated ghrelin concentration and sensations associated with appetite (Paper II). Study 3 included 28 patients with IBS randomly allocated to daily supplementation with 2.5 g CPH (n=13) or placebo (n=15) for 6 weeks. Outcomes were evaluated at baseline and after six weeks. Primary outcomes were symptom severity evaluated by IBS Severity Scoring System (IBS-SSS) and quality of life. Secondary outcomes included gut integrity markers (zonulin, lipopolysaccharide-binding protein, intestinal fatty acid binding protein) and pro-inflammatory cytokines in serum, fecal calprotectin and fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) (Paper IV). Results: No differences were observed between CPH and control for postprandial concentrations of glucose, GLP-1, acylated ghrelin or sensation related to appetite, but the postprandial insulin concentration was significantly lower after CPH compared to control (Study 1). No differences in estimated postprandial maximum level of glucose, insulin or GLP-1 were observed when comparing the dose of 10 mg/kg body weight of CPH to 20, 30 or 40 mg/kg body weight, but the estimated maximum value of glucose and insulin was lower for the 40 mg/kg body weight dose than the 10 mg/kg body weight dose (Study 2). Total IBS-SSS scores were reduced in both the CPH group and the placebo group, with no significant differences between intervention and placebo treatment. Concentrations of serum markers and SCFAs did not change for any of the groups (Study 3). Conclusion: Study 1 demonstrated that a single dose of CPH before a breakfast meal reduced the postprandial insulin concentration, without affecting blood glucose response, GLP-1 levels, concentrations of acylated ghrelin or sensations related to appetite in healthy individuals. Study 2 demonstrated that serum glucose and insulin concentrations tended to be reduced with increasing doses of CPH, however no significant effects were observed. Study 3 suggested that 2.5 g of CPH taken daily by IBS patients for six weeks did not affect symptom severity, gut integrity markers, inflammatory markers or fecal fermentation when compared to placebo

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

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.publishedVersio

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