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1.
Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome.
Hillestad, EMR, van der Meeren, A, Nagaraja, BH, Bjørsvik, BR, Haleem, N, Benitez-Paez, A, Sanz, Y, Hausken, T, Lied, GA, Lundervold, A, et al
World journal of gastroenterology. 2022;(4):412-431
Abstract
Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.
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2.
The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study.
Mazzawi, T, Hausken, T, Refsnes, PF, Hatlebakk, JG, Lied, GA
Microorganisms. 2022;(9)
Abstract
Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.
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3.
Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: recent developments and future perspectives.
Dale, HF, Lied, GA
Turkish journal of medical sciences. 2020;(SI-2):1632-1641
Abstract
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.
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4.
Probiotics in Irritable Bowel Syndrome: An Up-to-Date Systematic Review.
Dale, HF, Rasmussen, SH, Asiller, ÖÖ, Lied, GA
Nutrients. 2019;(9)
Abstract
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.
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5.
Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.
Mazzawi, T, Hausken, T, Hov, JR, Valeur, J, Sangnes, DA, El-Salhy, M, Gilja, OH, Hatlebakk, JG, Lied, GA
Scandinavian journal of gastroenterology. 2019;(6):690-699
Abstract
Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.
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6.
Erratum: Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial - CORRIGENDUM.
Dale, HF, Jensen, C, Hausken, T, Lied, E, Hatlebakk, JG, Brønstad, I, Hoff, DAL, Lied, GA
Journal of nutritional science. 2019;:e1
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Abstract
[This corrects the article DOI: 10.1017/jns.2018.23.].
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7.
Non-coeliac gluten sensitivity and the spectrum of gluten-related disorders: an updated overview.
Dale, HF, Biesiekierski, JR, Lied, GA
Nutrition research reviews. 2019;(1):28-37
Abstract
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.
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The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge.
Dale, HF, Hatlebakk, JG, Hovdenak, N, Ystad, SO, Lied, GA
Neurogastroenterology and motility. 2018
Abstract
BACKGROUND Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD). METHODS Twenty patients (14F/6M, age range: 21-62 years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0 g gluten) for 4 days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure. KEY RESULTS Collectively the whole group reported the most severe symptoms after placebo (P = .012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P = .029). CONCLUSIONS AND INFERENCES The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.
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Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome.
Hustoft, TN, Hausken, T, Ystad, SO, Valeur, J, Brokstad, K, Hatlebakk, JG, Lied, GA
Neurogastroenterology and motility. 2017;(4)
Abstract
BACKGROUND A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low-FODMAP vs high-fructo-oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short-chain fatty acids (SCFAs). METHODS Twenty patients with diarrhea-predominant or mixed IBS were instructed to follow a low-FODMAP diet (LFD) throughout a 9-week study period. After 3 weeks, they were randomized and double-blindly assigned to receive a supplement of either FOS (FODMAP) or maltodextrin (placebo) for the next 10 days, followed by a 3-week washout period before crossover. Irritable bowel syndrome severity scoring system (IBS-SSS) was used to evaluate symptoms. Cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor alpha) were analyzed in blood samples, and gut microbiota composition (16S rRNA) and SCFAs were analyzed in fecal samples. KEY RESULTS Irritable bowel syndrome symptoms consistently improved after 3 weeks of LFD, and significantly more participants reported symptom relief in response to placebo (80%) than FOS (30%). Serum levels of proinflammatory IL-6 and IL-8, as well as levels of fecal bacteria (Actinobacteria, Bifidobacterium, and Faecalibacterium prausnitzii), total SCFAs, and n-butyric acid, decreased significantly on the LFD as compared to baseline. Ten days of FOS supplementation increased the level of these bacteria, whereas levels of cytokines and SCFAs remained unchanged. CONCLUSIONS AND INFERENCES Our findings support the efficacy of a LFD in alleviating IBS symptoms, and show changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.
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10.
Indication of immune activation in patients with perceived food hypersensitivity.
Lied, GA
Digestive diseases and sciences. 2014;(2):259-66
Abstract
Majority of the patients with perceived food hypersensitivity have irritable bowel syndrome (IBS), and a significant proportion of IBS patients also attribute their gastrointestinal complaints to food items. Different factors such as disturbed intestinal fermentation, enteric dysmotility, post-infectious changes and altered microbial flora in the colon as well as psychological disturbances likely play a role in the pathophysiology and symptoms generation in patients with food hypersensitivity. In addition, a number of studies in these patient groups indicate that local, systemic and mucosal immune systems are activated. The question now is no longer intestinal immune activation, but how the immune system is activated in these patients. In the following review, the potential pathogenetic role of the immune system and evidence of immune activation are reported in patients with perceived food hypersensitivity.