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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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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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Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study.
Ostrowska, L, Wasiluk, D, Lieners, CFJ, Gałęcka, M, Bartnicka, A, Tveiten, D
Journal of clinical medicine. 2021;10(19)
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IBS, also known as irritable bowel syndrome, is a debilitating condition characterised by abdominal pain, irregular bowel movements, and changes in the consistency of stool. Symptoms of IBS may appear shortly after eating a meal. Excluding foods high in FODMAP carbohydrates, such as fermentable oligo- and di-saccharides, mono- and disaccharides, and polyols, or following an elimination rotation diet to reduce IgG-dependent food hypersensitivity, which has been shown to improve IBS symptoms previously. The purpose of this open-label study is to investigate the effectiveness of a low-FODMAPS diet and an elimination rotation diet based on IgG as well as a control diet in reducing symptoms of IBS. During the eight-week study, 73 female subjects with a mix of IBS were assigned to either of the three dietary treatments. Compared to the other diet groups, the IgG based elimination rotation diet group showed a significant improvement in the IBS symptoms and comorbid symptoms after the intervention period. In order to determine whether IgG-mediated food hypersensitivity plays a role in IBS and the efficacy of an IgG-dependent elimination rotation diet in the general population, further robust research is required. Healthcare professionals, however, can make use of these results to gain a better understanding of how an IgG based elimination diet tailored to each individual can improve IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- After implementing the three diets, among patients with IBS-M, a statistically significant reduction of the frequency of the idiopathic abdominal pain, abdominal pain after a meal, abdominal pain during defecation, and sensation of incomplete defecation before and after the diet plans, were only found in Group 2.
- Significantly, only in the Group 2 IgG based elimination-rotation-diet was there a high decrease or complete disappearance of dyspeptic IBS symptoms and co-morbidities together with IBS symptoms.
- This study shows that a personalised dietary approach is more effective in treating IBS than generalised diet recommendations, with elimination diets focused on IgG antibodies providing the best results.
Evidence Category:
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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:
Science supports the use of a low-FODMAP diet for symptom relief of IBS. However, more recently evidence suggests that IBS is a low-grade inflammatory disease that may result from or lead to IgG-dependent food hyper-sensitivities.
This study compared the effectiveness of three dietary treatment plans in 73 female patients diagnosed with mixed-form IBS based on Rome III criteria and no other gastrointestinal condition over 8 weeks.
The 3 dietary groups were:
- Group 1-low FODMAP diet
- Group 2- IgG based elimination-rotation-diet
- Group 3-control diet (control group)
Diets of G1 and G2 were determined individually by a dietitian, based on low-FODMAP dietary information and results from IgG food sensitivity testing respectively. Group 3 received nutrition advice from a gastroenterologist.
In G1, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). Gurgling sensation and gastric fullness also reach statistical significance in G1.
IBS symptoms as well as co-morbid symptoms significantly improved or disappeared completely in G2 (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008; sensation of incomplete defecation p = 0.001; difficulty to defecate (constipation) p = 0.002; bloating p = < 0.001; gurgling sensation < 0.001; gastric fullness p = < 0.001. However, blood and mucus in the stool were impossible to test because the symptoms were not reported by any patient during the 2nd examination). (p-values less than 0.05 were considered statistically significant).
In group G3 no statistically significant improvements were seen in any measure.
Based on the results of this open-label study, it was concluded that personalised dietary interventions were more effective in the treatment of IBS-M patients than generalised diet recommendations. Dietary elimination based on IgG food sensitivity test results had the greatest impact on IBS and related symptoms.This study supports results from other studies showing an IgG-guided diet as an effective strategy in co-morbid conditions such as fatigue, headache/migraine, and skin conditions.
Conflicts of Interest
C.F.J.L., M.G. and A.B. are employees of the Institute of Microecology in Poznan ,where the ImuPro tests were determined. D.T. is the Head of Laboratory and shareholder of Lab1, offering ImuPro tests in Norway.
Clinical practice applications:
- Low FODMAP diets studies (NICE) showed GI improvements for abdominal pain, abdominal cramps, diarrhoea, gas, and bloating, largely because FODMAPs mainly cause an excessive production of gas, leading to discomfort and pain and an increased osmotic effect leading to increased bowel movement and diarrhoea. However 30% of patients still suffered from bloating on the FODMAP diet. Gurgling sensation decreased from 65% to 15%, and gastric fullness decreased from 58% to 11% in the patients on the low FODMAP diet.
- A potential new approach to resolve functional symptoms of gastrointestinal conditions could be to start with an IgG-guided elimination diet, as it was proven to be the more effective diet in this open study, and in cases of persistent symptoms, it could be combined with a low-FODMAP diet.
- Calprotectin is currently one of the best-known diagnostic markers indicating mucosa inflammation and changes in the inflammation intensity. In this study serious intestinal inflammation was diagnosed at the faecal calprotectin concentration of >50 mg/kg of stool. During the first examination, no statistically significant differences were found in calprotectin concentrations between the compared groups of patients, and the values were low, suggesting that the included patients suffered from low-grade inflammation and were suitable for diet alteration as the best choice of treatment.
Limitations:
- The main limitations of this study are the open-labeled nature, the low number of participants and the bias of only including female participants with only the patients in the G2 group tested for IgG food antibodies.
- Foods consumed by the patients before they entered the study were not ascertained.
Considerations for future research:
- Claims that IgG food antibodies only reveal exposure to food and not intolerance should be reinvestigated in larger double-blinded studies.
Abstract
Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.
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Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review.
Aranburu, E, Matias, S, Simón, E, Larretxi, I, Martínez, O, Bustamante, MÁ, Fernández-Gil, MDP, Miranda, J
Nutrients. 2021;13(6)
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There is growing evidence that gluten and FODMAPs, such as fermentable oligosaccharides, disaccharides, monosaccharides and polyols, can cause gastrointestinal symptoms, inflammation, and immune responses in patients with celiac disease and irritable bowel syndrome. In addition, a high intake of gluten and FODMAPs may also be associated with neurological and psychiatric disorders. Thirteen studies were included in this systematic review to examine the relationship between gluten and FODMAP consumption and illnesses affecting the central nervous system. In addition, the studies examined the effects of potential dietary strategies that consider gluten and FODMAP intake on mental disorders, anxiety, depression, schizophrenia, Alzheimer’s disease, and autism spectrum disorders. Several possible mechanisms identified in this systematic review could contribute to neurological and psychiatric disorders, including the release of proinflammatory cytokines, immune responses, gut dysbiosis, intestinal permeability, and interactions between the gut-brain axis. In patients with fibromyalgia, celiac disease, and irritable bowel syndrome, avoiding or limiting gluten may reduce depression, anxiety, and cognitive impairment. However, the effects of a low-FODMAP diet on the central nervous system are inconclusive. There is some evidence that gluten-free diets can improve cognition in schizophrenia patients. In addition, those with autism spectrum disorders may benefit from a gluten-free diet and a low-FODMAP diet. Further robust research is required to evaluate the beneficial effects of interventions that avoid or restrict the consumption of foods high in FODMAPs and gluten. However, healthcare professionals can use the results of this systematic review to understand the potential benefits of therapeutic interventions that consider the intake of FODMAPs and gluten on illnesses affecting the central nervous system and their possible mechanisms of action.
Abstract
Nowadays, gluten and FODMAP food components (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are increasingly studied due to their possible relation with extraintestinal-associated conditions. In recent years, gluten-free diets (GFD) and low-FODMAP diets (LFD) are becoming more popular not only in order to avoid the food components that cause intolerances or allergies in some people, but also due to the direct influence of marketing movements or diet trends on feeding habits. Likewise, neurological and psychiatric diseases are currently of increasing importance in developed countries. For this reason, a bibliographic systematic review has been carried out to analyse whether there is a pathophysiological relationship between the dietary intake of gluten or FODMAPs with mental disorders. This review collects 13 clinical and randomized controlled trials, based on the PRISMA statement, which have been published in the last ten years. Based on these results, limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as depression, anxiety (7 out of 7 articles found any positive effect), or cognition deficiency (improvements in several cognition test measurements in one trial), and to a lesser extent for schizophrenia and the autism spectrum. Nevertheless, further studies are needed to obtain completely reliable conclusions.
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Effect of a short-term low fermentable oligiosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet on exercise-related gastrointestinal symptoms.
Wiffin, M, Smith, L, Antonio, J, Johnstone, J, Beasley, L, Roberts, J
Journal of the International Society of Sports Nutrition. 2019;16(1):1
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A diet high in fermentable oligosaccharides, disaccharides, monosaccharaides and polyols (FODMAPs) may result in altered gut motility. Research has shown that 30-50% of endurance athletes list gastrointestinal (GI) issues as a cause of underperformance, however there is little evidence on the impact of FODMAPs during endurance training. The aim of this randomised, crossover trial was to determine the effects of a short-term, low FODMAP diet on GI symptoms and perceived ability to exercise in 16 healthy volunteers. Participants were randomly assigned to either a low FODMAP diet or high FODMAP diet for seven days with a seven-day washout period. GI symptoms, perceived ability to exercise and markers of acute GI inflammation were recorded at the beginning and end of each intervention period. This study found a short-term, low FODMAP diet reduced exercise-related GI symptoms and improved perceived ability to exercise compared with a high FODMAP diet. Based on these results, the authors recommend the therapeutic benefits of a sustained low FODMAP diet in athletes be further explored.
Abstract
BACKGROUND Research has demonstrated that low fermentable oligiosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diets improve gastrointestinal (GI) symptoms in irritable bowel syndrome sufferers. Exercise-related GI issues are a common cause of underperformance, with current evidence focusing on the use of FODMAP approaches with recreationally competitive or highly trained athletes. However, there is a paucity of research exploring the potential benefit of FODMAP strategies to support healthy, recreational athletes who experience GI issues during training. This study therefore aimed to assess whether a short-term LOWFODMAP diet improved exercise-related GI symptoms and the perceived ability to exercise in recreational runners. METHODS Sixteen healthy volunteers were randomly assigned in a crossover design manner to either a LOWFODMAP (16.06 ± 1.79 g·d- 1) or HIGHFODMAP (38.65 ± 6.66 g·d- 1) diet for 7 days, with a one week washout period followed by a further 7 days on the alternate diet. Participants rated their gastrointestinal symptoms on an adapted version of the Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) questionnaire before and at the end of each dietary period. Perceived ability to exercise (frequency, intensity and duration) in relation to each dietary period was also rated using a visual analogue scale. Resting blood samples were collected prior to and on completion of each diet to determine plasma intestinal fatty acid binding protein (I-FABP) as a marker of acute GI injury. RESULTS Overall IBS-SSS score significantly reduced in the LOWFODMAP condition from 81.1 ± 16.4 to 31.3 ± 9.2 (arbitrary units; P = 0.004). Perceived exercise frequency (z = 2.309, P = 0.02) and intensity (z = 2.687, P = 0.007) was significantly improved following a short-term LOWFODMAP approach compared to HIGHFODMAP. No significant differences were reported between dietary conditions for plasma I-FABP (P > 0.05). CONCLUSIONS A short-term LOWFODMAP diet under free-living conditions reduced exercise-related GI symptoms and improved the perceived ability to exercise in otherwise healthy, recreational runners. These findings may be explained by a reduction in indigestible carbohydrates available for fermentation in the gut. The therapeutic benefits of LOWFODMAP diets in recreational and trained athletes during sustained training periods warrants further investigation.
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Pilot Study: Comparison of Sourdough Wheat Bread and Yeast-Fermented Wheat Bread in Individuals with Wheat Sensitivity and Irritable Bowel Syndrome.
Laatikainen, R, Koskenpato, J, Hongisto, SM, Loponen, J, Poussa, T, Huang, X, Sontag-Strohm, T, Salmenkari, H, Korpela, R
Nutrients. 2017;9(11)
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Among patients with irritable bowel syndrome (IBS), many report wheat-consumption related symptoms. There is an on-going debate as to whether IBS symptoms from wheat consumption are due to FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides and Polyols) or wheat proteins such as gluten. The aim of this randomised double-blind controlled study was to evaluate the impact of sourdough fermentation on wheat tolerance in 26 participants with IBS as well as changes in the molecular content of bread. Participants were randomised to consume 150 grams of either sourdough-fermented or yeast-fermented bread daily for one week and adhered to a gluten-free diet one week prior to the start of intervention and throughout the intervention. Blood samples were taken and gastrointestinal symptoms were recorded at baseline and post-intervention. The protein and FODMAP content of both types of bread was recorded as well. This study found sourdough fermentation reduced both the quantities of wheat proteins and FODMAPs significantly, however was not tolerated symptomatically any better than yeast-fermented bread. This sheds light on the fact that studies using unfermented wheat products cannot necessarily be extrapolated to fermented wheat products such as sourdough bread. Based on these results, the authors conclude further large-scale clinical studies are required to better classify the role of wheat proteins in functional gastrointestinal disorders.
Abstract
Many patients suspect wheat as being a major trigger of their irritable bowel syndrome (IBS) symptoms. Our aim was to evaluate whether sourdough wheat bread baked without baking improvers and using a long dough fermentation time (>12 h), would result in lower quantities of alpha-amylase/trypsin inhibitors (ATIs) and Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs), and would be better tolerated than yeast-fermented wheat bread for subjects with IBS who have a poor subjective tolerance to wheat. The study was conducted as a randomised double-blind controlled 7-day study (n = 26). Tetrameric ATI structures were unravelled in both breads vs. baking flour, but the overall reduction in ATIs to their monomeric form was higher in the sourdough bread group. Sourdough bread was also lower in FODMAPs. However, no significant differences in gastrointestinal symptoms and markers of low-grade inflammation were found between the study breads. There were significantly more feelings of tiredness, joint symptoms, and decreased alertness when the participants ate the sourdough bread (p ≤ 0.03), but these results should be interpreted with caution. Our novel finding was that sourdough baking reduces the quantities of both ATIs and FODMAPs found in wheat. Nonetheless, the sourdough bread was not tolerated better than the yeast-fermented bread.