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Effects of FODMAPs and Gluten on Gut Microbiota and Their Association with the Metabolome in Irritable Bowel Syndrome: A Double-Blind, Randomized, Cross-Over Intervention Study.
Nordin, E, Hellström, PM, Dicksved, J, Pelve, E, Landberg, R, Brunius, C
Nutrients. 2023;15(13)
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Irritable bowel syndrome (IBS) is defined as recurring abdominal pain in relation to stool irregularities. The mechanisms behind IBS are poorly understood, but changes in gut microbiota composition, intestinal barrier function, enteroendocrine cell population, low-grade inflammation and gut–brain axis modulations are believed to play a role. The aim of this study was to investigate how fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. This study was a double-blind, placebo-controlled three-way crossover study. Both the study personnel and participants were blinded. Results showed that consumption of high FODMAP foods, but not gluten, altered the gut microbiota composition, in particular causing changes to microbiota and metabolites, previously associated with improved metabolic health and reduced inflammation. There were also minor effects of FODMAPs and gluten on short-chain fatty acids. Authors conclude that the intake of FODMAP, but not gluten, over one week altered the gut microbiota composition, with only weak associations with IBS symptoms. Healthcare practitioners working with IBS should consider the impacts on the gut microbiome when advising the use of a low-FODMAP diet.
Abstract
BACKGROUND A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. METHODS We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. RESULTS FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. CONCLUSIONS FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.
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Effects of a low FODMAP diet on gut microbiota in individuals with treated coeliac disease having persistent gastrointestinal symptoms - a randomised controlled trial.
Herfindal, AM, van Megen, F, Gilde, MKO, Valeur, J, Rudi, K, Skodje, GI, Lundin, KEA, Henriksen, C, Bøhn, SK
The British journal of nutrition. 2023;130(12):2061-2075
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Coeliac disease (CeD) is a common immune-mediated disease where intolerance to gluten can lead to severe health problems with a wide range of gastrointestinal (GI) and extra-intestinal symptoms. Research shows that a diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) helps to reduce GI symptoms in irritable-bowel syndrome and gluten-free diet treated CeD. The aim of this study was to investigate whether a low FODMAP diet (LFD) in this patient group affects (i) the faecal microbiota, (ii) the concentrations of faecal short-chain fatty acids (SCFA) and (iii) the concentrations of faecal human neutrophil gelatinase-associated lipocalin (a biomarker of gut inflammation). This study is part of a clinical trial which followed a nonblinded, parallel randomised design. The participants were randomised to either an LFD group or a control group. Results showed that after four weeks, certain differences in gut microbiota were detected between the control and LFD group. The SCFA results indicated that the LFD resulted in lower concentrations of propionic and valeric acid in participants with initially high concentrations. Biomarker of gut inflammation was, however, unaffected by the LFD. Authors conclude that the LFD led to changes in overall community structure of the faecal microbiota, with a possible unfavourable low faecal abundance of Anaerostipes, and low concentrations of the faecal SCFA propionic and valeric acid in participants with high concentrations of these acids at baseline.
Abstract
Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject β-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).
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The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review.
Osowiecka, K, Myszkowska-Ryciak, J
Nutrients. 2023;15(4)
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Hashimoto’s thyroiditis is an autoimmune disorder characterized by the presence of antibodies in the thyroid gland such as thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies. Immune-mediated inflammatory responses eventually lead to the progressive destruction of the gland and impaired thyroid function. The disease has a strong genetic disposition but is also influenced by environmental factors, including diet. Hence diet has been considered a complementary tool to manage thyroid function and disease progression by harnessing the benefits of certain nutrients and anti-inflammatory properties. This systematic review examined the effects of nutrients and dietary interventions on Hashimoto’s disease in current literature. Using antibody levels, thyroid hormone levels and body weight to measure outcomes. The review included 9 studies, all of which compared the intervention group to the control groups. The trials included looked at gluten-free, lactose-free and energy-restricted diets, with or without selected nutrients and foods supplements (ie. Nigella sativa, iodine). The intervention duration ranged from 3 weeks to 12 months. Despite the small number of trials, the data from those studies included in this review showed promising results. Improvements in disease parameters were observed in diets that were energy deficient, eliminated gluten, lactose and goitrogens or added Nigella sativa. Iodine restrictions did not show any improvements. In the discussion section, the authors presented the results in the wider context and the findings from other studies. Ultimately there appears to be a wide variance in outcomes, usually ranging from beneficial to neutral. The authors contributed to such variability due to the complexity of the condition and many influencing factors. Often participants in trials have highly variable thyroid status and function, and differences in regular dietary intakes of nutrients critical to thyroid health can easily distort the results. Hence much more specific research is needed to make firmer conclusions. Whereby no clear conclusions in larger groups could be drawn, potential benefits of dietary interventions in Hashimoto's disease may be much more apparent in clinical settings with personalized approaches that account for such individual variances.
Abstract
Diet can be a complementary treatment for Hashimoto's disease by affecting thyroid function and anti-inflammatory properties. It is still unclear which dietary strategy would be the most beneficial. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody and thyroid hormones levels) and characteristic symptoms in the course of Hashimoto's thyroiditis. This systematic review was prepared based on PRISMA guidelines. Articles in PubMed and Scopus databases published up to November 2022 were searched. As a result of the selection, out of 1350 publications, 9 were included for further analysis. The nutritional interventions included the following: elimination of gluten (3 articles) or lactose (1 article), energy restriction with or without excluding selected foods (n = 2), consumption of Nigella sativa (n = 2), or dietary iodine restriction (n = 1). The intervention duration ranged from 21 days to 12 months and included individuals with various thyroid function. Of the nine studies, three studies were female only. An improvement was observed during an energy deficit and after the elimination of selected ingredients (e.g., gluten, lactose, or goitrogens), as well as after the intervention of Nigella sativa. These interventions improved antibody levels against peroxidase (anti-TPO), (thyrotropin) TSH, and free thyroxine (fT4). No improvement was seen on the iodine-restricted diet. Varied outcomes of analyzed dietary interventions may be due to the heterogeneous thyroid condition, high variability between patients, and differences in habitual intake of critical nutrients (e.g., iodine, selenium, and iron) in different populations. Therefore, there is a great need for further experimental studies to determine whether any nutritional interventions are beneficial in Hashimoto's disease.
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Helping psoriasis from the inside out
Dr. Mark Hyman is a practicing family physician and an internationally recognised leader, speaker, educator, and advocate in the field of Functional Medicine. He is the founder and director of The UltraWellness Centre, the Head of Strategy and Innovation of the Cleveland Clinic Centre for Functional Medicine, a thirteen-time New York Times bestselling author, and Board President for Clinical Affairs for The Institute for Functional Medicine.
2022
Abstract
In this podcast episode Dr Hyman speaks to Dr Todd LePine about the various causes of psoriasis including genetics, diet, environmental factors, toxins, and streptococcus bacteria, highlighting that psoriasis is not a skin condition but rather a systemic one. They review both the conventional and functional medicine approaches to manage psoriasis, sharing interesting patient case studies and solutions that have worked which primarily centre around addressing gut health. Key functional laboratory tests to identify the root causes of psoriasis are reviewed but they highlight that it is also important to discuss stress, sleep and sun exposure with patients due to their impact on the immune system and subsequent gut integrity.
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The role of gut health in psoriasis
Alex Manos is one of the UK’s leading Functional Medicine practitioners who specialises in SIBO and gut-related disorders, as well as mould illness and mycotoxins. He is also very passionate about physical therapy, movement, resiliency, life coaching, nutritional therapy, and biohacking. He is a lecturer at various colleges and institutions including the Institute of Optimum Nutrition (ION) and on the MSc program at The Centre For Nutritional Education and Lifestyle Management (CNELM).
2022
Abstract
This is a really informative and concise presentation (with slides) from Alex summarising the research around the role of gut health in psoriasis. He covers dysbiosis, gut microbiome metabolites, gut inflammation, small intestinal bacterial overgrowth (SIBO), leaky gut and also coeliac and gluten sensitivity. He is quick to point out however that the gut is not the only thing that contributes to psoriasis, as there are many factors that can accumulate and contribute to psoriasis including infections, body composition, environmental toxins, medications, poor diet, and stress. He addresses testing options that are available to help determine which aspect of gut health could be targeted using nutrition and supplements to help alleviate the severity of psoriasis.
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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome.
Algera, JP, Magnusson, MK, Öhman, L, Störsrud, S, Simrén, M, Törnblom, H
Alimentary pharmacology & therapeutics. 2022;56(9):1318-1327
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The majority of irritable bowel syndrome (IBS) patients relate their symptoms to intake of certain foods. The gut microenvironment, where microbiota, food components and the nervous system interact, is suggested to play a key role in gastrointestinal (GI) symptom generation in a subset of IBS patients. The main aim of this study was to assess and compare the efficacy of the gluten-free and gluten-containing diets in terms of effects on GI symptoms in IBS patients. Secondary aims where to identify the putative link between gut microenvironment and the diets´ effect on GI symptoms, and to identify potential predictors of clinical response to the gluten-free diet. This study is a single-centre, double-blind, randomised, placebo-controlled, cross-over trial. Adult sex- and age-matched IBS patients (n=20) and healthy controls (HC) (n=21) were recruited, randomised and challenged with gluten (14 g/day) and rice flour, both for 2 weeks, while adhering to a strict gluten-free diet. Results indicate that a gluten-free diet may affect IBS symptoms in general, and bowel habits in a subset of IBS patients. The gluten-free diet has distinct effect on the gut microenvironment in IBS patients who respond favourably to gluten reduction. Authors conclude that the gut microenvironment may be of importance in the clinical response to the gluten-free diet in IBS, and future studies should aim to further assess these factors in relation to clinical response to the gluten-free diet.
Abstract
BACKGROUND A gluten-free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms. AIMS To assess the effects of gluten-free versus gluten-containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the gluten-free diet in IBS METHODS Twenty patients with IBS and 18 healthy controls (HC) followed a gluten-free diet during two 14-day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS-SSS) and bowel habits. Secondary outcomes included effects of gluten-free diet on faecal microbiota and metabolite profile. RESULTS IBS symptoms improved during the gluten-free (p = 0.02), but not the gluten-containing period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten-free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten-free diet (p < 0.001). True responders (reduced IBS-SSS by ≥50 solely after gluten-free period) and non-responders were discriminated based on the effects of the gluten-free diet on the microbiota (p < 0.01) and metabolite profiles (p < 0.001). The response to the gluten-free diet could be predicted by the metabolite profile before the intervention (p < 0.001). CONCLUSIONS A gluten-free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten-free diet seems to impact the gut microenvironment. Responsiveness to the gluten-free diet may be predicted by the metabolite profile. CLINICALTRIALS gov: NCT03869359.
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Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet.
Rej, A, Sanders, DS, Shaw, CC, Buckle, R, Trott, N, Agrawal, A, Aziz, I
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;20(12):2876-2887.e15
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Irritable bowel syndrome (IBS) is a common disorder characterised by stomach pain, bloating, and altered bowel movements. Dietary therapy is a way to manage IBS, with 3 diets becoming popular amongst health care professionals and those who suffer from IBS. Traditional dietary advice (TD), which involves adopting healthy, sensible eating patterns with adequate hydration, is the first line recommendation in the UK. The low-FODMAP diet (LFD) is the avoidance of carbohydrates, which tend to ferment in the stomach and are found in certain fruits and vegetables. The gluten free diet (GFD) is the avoidance of foods which contain gluten such as bread and pasta. All three diets have little evidence to support their use in IBS and this randomised control trial of 101 individuals with IBS aimed to determine whether the GFD and LFD are superior in relieving IBS symptoms compared to TD. The results showed that GFD, LFD and TD were all effective in the management of non-constipated IBS, but that TD was easier to follow and cheaper compared to the other two diets. It was concluded that TD should be used as first-line therapy for people with non-constipated IBS and that GFD and LFD should be reserved for specific patients under the care of a health care professional.
Expert Review
Conflicts of interest:
None
Take Home Message:
- TDA, LFD and GFD can all lead to significant improvements in non-constipation IBS with no statistically significant difference in effectiveness between the diets.
- Most patients find a TDA easier and cheaper to implement than a LFD or GFD.
- TDA is therefore recommended as a first line approach in non-constipation IBS.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The aim of this study was to compare the effectiveness and patient acceptability of traditional dietary advice (TDA) vs a low FODMAP diet (LFD) vs a gluten-free diet (GFD, cross-contamination allowed) in patients with non-constipation irritable bowel syndrome (IBS).
TDA definition: healthy, sensible eating pattern, including regular meals, not eating too little/too much, adequate hydration, and reducing the intake of: alcohol/caffeine/fizzydrinks/fatty/spicy/ processed foods; fresh fruit (maximum of 3 per day); fibre/gas-producing foods and perceived food intolerances.
Methods
This was a randomised dietary trial over 4 weeks. Dietary advice was provided by a specialist dietitian in a session lasting 45-60 minutes. 99 patients completed the study (33 in each group). Stool analysis was performed in “around half“ (study authors terminology) of participants due to disruption of trial caused by COVID-19.
Results:
- Primary endpoint (reduction of 50 points or more on IBS symptom severity score) was met by 42% of patients on the TDA, 55% on LFD and 58% on GFD. The differences between groups were not statistically significant, p=0.43.
- Patients on the LFD had greater improvements in mood compared to the other diets under examination, reaching statistical significance (p=0.03) for Hospital Anxiety and Depression scale and (p<0.01) for dysphoria score on IBS-QOL scale.
- Patients on TDA found their diet cheaper (p<0.01), less time consuming to shop (p<0.01) and easier to follow when eating out with family and friends (p=0.03), whilst TDA and GFD were considered easier to incorporate into daily diet than LFD (p=0.02).
- No significant differences were found between groups in changes to macro- and micronutrient composition, except a trend to lower fibre intake with LFD (p=0.06).
- There was a significant reduction in intake of FODMAPs in all groups, with greatest reduction in LFD (27.7 to 7.6 g/day, p<0.01), followed by TDA (24.9 to 15.2 g/day, p<0.01) and GFD (27.4 to 22.4 g/day, p=0.03). Differences between groups were statistically significant (p<0.01).
- No differences were noted in change to the dysbiosis index between groups.
- Neither clinical characteristics nor dysbiosis index predicted response to any of the diets.
Conclusion
- TDA, LFD and GFD are all effective approaches for non-constipation IBS.
- TDA should be first-line dietary advice due to being the most patient-friendly.
Clinical practice applications:
- When working with clients with non-constipation IBS, a TDA approach may be favoured over LFD and GFD as a first line intervention if the patient has not already tried a TDA diet.
- Patient preferences, budget, time and living situation should be taken into account when deciding on best dietary advice for IBS.
Considerations for future research:
- As all 3 approaches led to reduction in FODMAPs, trials comparing different levels of FODMAP exclusion could lead to valuable information, as a strict FODMAP exclusion, which is commonly recommended in IBS, is difficult and may not be necessary.
- Studies of longer duration would be valuable to confirm that benefits observed with the 3 approaches are not short-term only.
- Comparing individual approaches to appropriate control group would ensure that improvements are not due to a placebo effect.
Abstract
BACKGROUND & AIMS Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD). METHODS Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination). The primary end point was clinical response after 4 weeks of dietary intervention, as defined by ≥50-point reduction in IBS symptom severity score (IBS-SSS). Secondary end points included (1) changes in individual IBS-SSS items within clinical responders, (2) acceptability and food-related quality of life with dietary therapy, (3) changes in nutritional intake, (4) alterations in stool dysbiosis index, and (5) baseline factors associated with clinical response. RESULTS The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n = 14/33) undertaking TDA, 55% (n = 18/33) for LFD, and 58% (n = 19/33) for GFD (P = .43). Responders had similar improvements in IBS-SSS items regardless of their allocated diet. Individuals found TDA cheaper (P < .01), less time-consuming to shop (P < .01), and easier to follow when eating out (P = .03) than the GFD and LFD. TDA was also easier to incorporate into daily life than the LFD (P = .02). Overall reductions in micronutrient and macronutrient intake did not significantly differ across the diets. However, the LFD group had the greatest reduction in total FODMAP content (27.7 g/day before intervention to 7.6 g/day at week 4) compared with the GFD (27.4 g/day to 22.4 g/day) and TDA (24.9 g/day to 15.2 g/day) (P < .01). Alterations in stool dysbiosis index were similar across the diets, with 22%-29% showing reduced dysbiosis, 35%-39% no change, and 35%-40% increased dysbiosis (P = .99). Baseline clinical characteristics and stool dysbiosis index did not predict response to dietary therapy. CONCLUSIONS TDA, LFD, and GFD are effective approaches in non-constipated IBS, but TDA is the most patient-friendly in terms of cost and convenience. We recommend TDA as the first-choice dietary therapy in non-constipated IBS, with LFD and GFD reserved according to specific patient preferences and specialist dietetic input. CLINICALTRIALS gov: NCT04072991.
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Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial.
Nordin, E, Brunius, C, Landberg, R, Hellström, PM
The American journal of clinical nutrition. 2022;115(2):344-352
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Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is characterised by recurring abdominal pain over ≥3 months within a 6-month period in association with altered bowel habits. Symptomatic treatment of IBS includes dietary adaptation, with a focus on prebiotics, probiotics, gluten, and fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). The main aim of this study was to investigate the effects of weeklong interventions with high intakes of a wide range of FODMAPs, gluten, or a nonfermentable placebo in subjects with moderate to severe IBS. This study is a double-blind, placebo-controlled, randomised 3-way study with triple crossover design. One-hundred and ten participants were enrolled and randomly assigned for the study. Results show that a mixture of widely consumed FODMAPs caused only modest worsening of gastrointestinal symptoms compared with gluten and placebo. Authors conclude that there were interindividual variability in the intervention responses. Thus, future studies should investigate these differences to understand possible underlying disease mechanisms.
Abstract
BACKGROUND Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. OBJECTIVES The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS). METHODS The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis. RESULTS In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P = 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported. CONCLUSION In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689.
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The effect of gluten in adolescents and young adults with gastrointestinal symptoms: a blinded randomised cross-over trial.
Crawley, C, Savino, N, Halby, C, Sander, SD, Andersen, AN, Arumugam, M, Murray, J, Christensen, R, Husby, S
Alimentary pharmacology & therapeutics. 2022;55(9):1116-1127
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The gluten-free diet (GFD) has gained increasing popularity among healthy people without coeliac disease or wheat allergy. The main reasons for following a GFD are weight control, the perception that a GFD is healthier, and the presence of symptoms after gluten ingestion. The aim of this study was to address the hypothesis that adding gluten to the diet results in a self-reported worsening of gastrointestinal symptoms (primary outcome) and mental health (key secondary outcomes) in a well-characterised group of adolescents. This study was arranged in two phases; the first phase began with 2 weeks of a GFD, and if the participants responded to the GFD, they proceeded to phase 2. Phase 2 was a double-blinded randomised trial with cross-over and consisted of three periods, each lasting 7 days: (1) a challenge with gluten/placebo, (2) wash-out phase, and (3) the second challenge with placebo/gluten. Results show that it was not possible to detect a difference in symptoms between gluten and placebo at a group level. Furthermore, on an individual level, there was a comparable number of gluten responders and placebo responders, underscoring the insignificant difference between gluten and placebo. Authors conclude that adding gluten to the diet does not induce gastrointestinal symptoms or worsened mental health in adolescents.
Abstract
BACKGROUND The popularity of the gluten-free diet and sales of gluten-free products have increased immensely. AIMS To investigate whether gluten induces gastrointestinal symptoms, measured by self-reported questionnaires, as well as mental health symptoms in adolescents from a population-based cohort. METHODS The eligible participants (n = 273) were recruited from a population-based cohort of 1266 adolescents and had at least four different gastrointestinal symptoms. Phase one (n = 54) was a run-in phase where the participants lived gluten-free for 2 weeks. If they improved they continued to phase 2 (n = 33), a blinded randomised cross-over trial. Participants were blindly randomised either to start with 7 days of gluten, eating two granola bars containing 10 g of gluten or to 7 days on placebo, eating two granola bars without gluten, followed by the reverse and separated by a 7-day washout period. The effects of the intervention on gastrointestinal symptoms and mental health symptoms were assessed. RESULTS In total, 54/273 participants entered the run-in phase and 35 were eligible for randomization. A total of 33 were randomised and 32 completed the trial. The median age was 20.3 (IQR 19.2-20.9) and 32/33 participants were females. Compared with a placebo, gluten did not induce gastrointestinal symptoms. The difference in the average VAS was -0.01 (95% confidence interval -2.07 to 2.05). Nor did we find a difference in the outcomes measuring mental health. CONCLUSION Compared with placebo, adding gluten to the diet did not induce gastrointestinal symptoms or worsened mental health in adolescents recruited from a population-based cohort. The trial registration number is NCT04639921.