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Diarrhoea of unknown cause: medical treatment in a stepwise mannerManagement of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment.
Jansson-Rehnberg, AS, Drewes, AM, Sponheim, J, Borgfelt, C, Münch, A, Graf, W, Simrén, M, Lindberg, G, Hellström, PM
Scandinavian journal of gastroenterology. 2024;:1-4
Abstract
The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
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A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARBIS): a single-centre, single-blind, randomised controlled trial.
Nybacka, S, Törnblom, H, Josefsson, A, Hreinsson, JP, Böhn, L, Frändemark, Å, Weznaver, C, Störsrud, S, Simrén, M
The lancet. Gastroenterology & hepatology. 2024
Abstract
BACKGROUND Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment with pharmacological treatment targeting the predominant IBS symptom. We therefore aimed to compare the effects of two restrictive dietary treatment options versus optimised medical treatment in people with IBS. METHODS This single-centre, single-blind, randomised controlled trial was conducted in a specialised outpatient clinic at the Sahlgrenska University Hospital, Gothenburg, Sweden. Participants (aged ≥18 years) with moderate-to-severe IBS (Rome IV; IBS Severity Scoring System [IBS-SSS] ≥175) and no other serious diseases or food allergies were randomly assigned (1:1:1) by web-based randomisation to receive a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) plus traditional IBS dietary advice recommended by the UK National Institute for Health and Care Excellence (hereafter the LFTD diet), a fibre-optimised diet low in total carbohydrates and high in protein and fat (hereafter the low-carbohydrate diet), or optimised medical treatment based on predominant IBS symptom. Participants were masked to the names of the diets, but the pharmacological treatment was open-label. The intervention lasted 4 weeks, after which time participants in the dietary interventions were unmasked to their diets and encouraged to continue during 6 months' follow-up, participants in the LFTD group were instructed on how to reintroduce FODMAPs, and participants receiving pharmacological treatment were offered diet counselling and to continue with their medication. The primary endpoint was the proportion of participants who responded to the 4-week intervention, defined as a reduction of 50 or more in IBS-SSS relative to baseline, and was analysed per modified intention-to-treat (ie, all participants who started the intervention). Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02970591, and is complete. FINDINGS Between Jan 24, 2017, and Sept 2, 2021, 1104 participants were assessed for eligibility and 304 were randomly assigned. Ten participants did not receive their intervention after randomisation and thus 294 participants were included in the modified intention-to-treat population (96 assigned to the LFTD diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment). 241 (82%) of 294 participants were women and 53 (18%) were men and the mean age was 38 (SD 13). After 4 weeks, 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group had a reduction of 50 or more in IBS-SSS compared with baseline, with a significant difference between the groups (p=0·023). 91 (95%) of 96 participants completed 4 weeks in the LFTD group, 92 (95%) of 97 completed 4 weeks in the low-carbohydrate group, and 91 (90%) of 101 completed 4 weeks in the optimised medical treatment group. Two individuals in each of the intervention groups stated that adverse events were the reason for discontinuing the 4-week intervention. Five (5%) of 91 participants in the optimised medical treatment group stopped treatment prematurely due to side-effects. No serious adverse events or treatment-related deaths occurred. INTERPRETATION Two 4-week dietary interventions and optimised medical treatment reduced the severity of IBS symptoms, with a larger effect size in the diet groups. Dietary interventions might be considered as an initial treatment for patients with IBS. Research is needed to enable personalised treatment strategies. FUNDING The Healthcare Board Region Västra Götaland, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, AFA Insurance, grants from the Swedish state, the Wilhelm and Martina Lundgren Science Foundation, Skandia, the Dietary Science Foundation, and the Nanna Swartz Foundation.
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Mechanisms underlying food-related symptoms in disorders of gut-brain interaction: Course ahead in research and clinical practice.
Colomier, E, Algera, JP, Van den Houte, K, Simrén, M, Tack, J
Best practice & research. Clinical gastroenterology. 2023;:101824
Abstract
A subgroup of patients with a disorder of gut-brain interaction (DGBI) report symptoms such as abdominal pain, gas-related symptoms, dyspeptic symptoms and loose stool or urgency after meal intake. Therefore, the effect of several dietary therapies including fibre-rich or restrictive diets have already been studied in patients with irritable bowel syndrome, functional abdominal bloating or distention, and functional dyspepsia. However, there is a paucity of studies in the literature on the mechanisms underlying food-related symptoms. Therefore, this review focuses on these potential mechanisms and explains the role of nutrient sensing and tasting, physical considerations, malabsorption or allergy-like reaction to food and its interaction with microbiota. In addition, it emphasizes the importance of future research and clinical practice regarding food-related symptoms in patients with a DGBI.
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Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis.
Bosman, M, Smeets, F, Elsenbruch, S, Tack, J, Simrén, M, Talley, N, Winkens, B, Masclee, A, Keszthelyi, D
Neurogastroenterology and motility. 2023;(2):e14474
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Abstract
BACKGROUND Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. METHODS We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. KEY RESULTS We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. CONCLUSIONS AND INFERENCES The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
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Irritable bowel syndrome with food-related symptoms: Future directions in the clinical management.
Melchior, C, Algera, J, Colomier, E, Törnblom, H, Simrén, M
United European gastroenterology journal. 2022;(6):594-600
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Abstract
The majority of patients with irritable bowel syndrome (IBS) experiences food-related symptoms, which are associated with high symptom burden, reduced quality of life, increased healthcare consumption and reduced intake of certain nutrients. In this review we aimed to describe a clinically useful approach for physicians, by presenting the latest progress in knowledge and its translation to management in IBS patients with food-related symptoms, as well as the underlying mechanisms involved. The research tools currently available that can be used in the future for a better characterization of this subgroup of patients are also discussed. Working towards this approach could lead to a more individualised work-up and management of IBS patients with food-related symptoms.
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Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.
Colomier, E, Van Oudenhove, L, Tack, J, Böhn, L, Bennet, S, Nybacka, S, Störsrud, S, Öhman, L, Törnblom, H, Simrén, M
Nutrients. 2022;14(2)
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Plain language summary
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction, formerly known as a functional gastrointestinal (GI) disorder. Apart from abdominal pain, altered stool frequency, diarrhoea, and constipation, a large proportion of patients with IBS also experience other GI symptoms such as abdominal distention, bloating and flatulence. The aim of this study was to investigate predictors of treatment response to the low FODMAP (short-chain carbohydrates, i.e., fermentable oligo-, di-, monosaccharides, and polyols) and the traditional IBS diet while focusing on the four core IBS symptoms (bloating, constipation, diarrhoea, and pain). This study was a post-hoc analysis of a previously published randomised controlled trial. In total, 33 patients on low FODMAP diet and 34 patients on the traditional IBS diet were included in the analysis. Results showed that patterns of psychological, dietary, and microbial factors can predict IBS symptom response to two dietary advice systems—the traditional IBS and the low FODMAP diet. A clinical profile with less severe IBS features appears to predict a better symptom-specific response to both dietary interventions. Authors conclude that larger prospective randomised controlled trials which include different treatment approaches are required as they may help to optimize personalized treatment algorithms in IBS.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary intervention for IBS related symptoms was efficacious for up to 75% of patients in this study
- Recommendation for a traditional IBS dietary intervention should supersede the low-FODMAP diet, with the latter only implemented when symptoms persist.
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
This randomised controlled intervention study of 67 individuals fulfilling the Rome III criteria for IBS drew comparisons between the efficacy of the traditional IBS diet - as directed by the British Dietetic Association and National Institute for Health and Care Excellence (NICE) - and the low fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) diet on specific IBS-related symptoms (pain, constipation, diarrhoea, and bloating).
Methods
A 10-day screening period included faecal sample analysis, 4-day food diary (pre-randomisation and last week of intervention), and daily stool diary (Bristol Stool Form scale). After 10 days, patients compiled several GI and non-GI related questionnaires, inclusive of IBS severity scoring system (IBS-SSS). Patients who scored ≥175 for the IBS-SSS were randomly allocated to follow either a low-FODMAP or traditional IBS diet for a period of 4-weeks. Thorough explanations were provided by trained Dietitians. During intervention, patients compiled symptom questionnaires (Gastrointestinal Symptoms Rating Scale-IBS) on a weekly basis.
Results
- Both diets reduced symptoms of pain, diarrhoea and bloating (all p<0.0001), but not constipation (p=0.15)
- There was no difference between following the traditional IBS diet and low-FODMAP diet in terms of pain (p=0.80), constipation (p=0.63), diarrhoea (p=0.96) and bloating (p=0.35)
- Less severe gut dysbiosis was weakly associated with better dietary response and improvement of constipation (p=0.05)
- Higher energy intake at baseline predicted better pain improvement with both dietary types compared to lower energy intake (p=0.03)
- More severe psychological distress predicted worse intervention response for bloating (p=0.03)
- Higher baseline oligosaccharide intake predicted a worse response to the low FODMAP diet (p=0.01) but not the traditional IBS diet (p=0.16).
Conclusion
This study demonstrated that based on 4 distinct IBS-related symptomatology, better treatment response to 2 different dietary strategies was noted in patients with less severe clinical characteristics. Higher energy intake at baseline and gut dysbiosis scores that were similar to healthy controls were associated with better improvements following dietary interventions. Thus patients who already follow a calorie restricted diet and who have more significant gut dysbiosis profiles might need more bespoke intervention. Severe psychological distress patients responded worse to both diets.
Clinical practice applications:
- Even a short 4-week specific dietary intervention (low FODMAP or traditional IBS diet) can result in IBS-related symptomatic improvement for pain, bloating, and diarrhoea, but not constipation
- The preferred starting point for dietary intervention should be the traditional IBS diet given its relative ease to follow
- The more restrictive low FODMAP protocol could be considered if symptoms persist
- More bespoke interventions are required for patients who suffer with severe psychological stress, have tested and found gut dysbiosis, and individuals who already follow a restrictive diet.
Considerations for future research:
- Future studies need to include not only larger but more diverse cultural and socio-economic cohorts to ascertain the efficacy of IBS symptom-related dietary interventions
- Longer periods of intervention are needed to confirm dietary intervention efficacy.
Abstract
(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.
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Low FODMAP diet reduces gastrointestinal symptoms in irritable bowel syndrome and clinical response could be predicted by symptom severity: A randomized crossover trial.
Algera, JP, Demir, D, Törnblom, H, Nybacka, S, Simrén, M, Störsrud, S
Clinical nutrition (Edinburgh, Scotland). 2022;41(12):2792-2800
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Plain language summary
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterised by chronic abdominal pain and altered bowel habits. Currently, many patients follow an exclusion diet where specific food components are eliminated. One of these exclusion diets is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). The primary aim of this study was to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms in IBS. This study was a double-blind, randomised, controlled, crossover study which enrolled 31 participants who were randomly assigned to the diet periods. Results showed that the severity of GI symptoms was reduced, and bowel habits were affected in the direction of less frequent and firmer stool by the low FODMAP diet, but not by a diet with moderate amounts of FODMAPs. Authors conclude that assessment of overall IBS severity and predominant bowel habits before the intervention may be helpful for clinicians in their IBS management before considering a trial period with the low FODMAP diet as a treatment option.
Expert Review
Conflicts of interest:
None
Take Home Message:
A low (4 g/day) FODMAP diet could provide clinical benefits in the context of an acute strategy for IBS clients with frequent loose stools (IBS-Diarrhoea and/or IBS-Mixed) compared to those with hard and less frequent stools (IBS-Constipation) to improve the severity of GI symptoms, including lower abdominal pain intensity and frequency, bowel habits, daily life interference, and psychological distress.
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 paper was to investigate the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in Irritable Bowel Syndrome (IBS).
Methods
- This study involved a double-blind, randomised, controlled, crossover trial of 29 participants (18-75 years), mostly female, diagnosed with IBS (Rome IV)
- The primary outcome was to assess the effects of a low (4 g/day) vs. moderate (23 g/day) FODMAP diet on GI symptoms over a 7-day period
- Secondary outcomes involved assessing the effects of low vs. moderate FODMAP diets on i) somatic symptoms, ii) psychological distress, iii) predictors of clinical and IBS-Severity Scoring System (IBS-SSS) sensitivity to FODMAP
- Breakfast was standardised, with prescribed low FODMAP list deviations recorded
- Main dishes and snacks were also provided
- Participants were requested to limit alcohol, caffeine, fatty- and spicy foods, ate regularly, chewed thoroughly and drank enough water
- GI symptoms and bowel habits were recorded during the 7-day screening period, then participants undertook a Lactulose Nutrient Challenge Test (LNCT)
- The first 7-day diet started one day after the LNCT
- A 14-day wash-out period allowed participants to eat and drink as usual, thereafter following the second 7-day diet period as part of the cross over design.
Results
A low FODMAP intervention (compared to a moderate FODMAP diet); resulted in:
- Reduced overall IBS rating (10 ± 72 vs. 57 ± 108, P=0.04)
- Improved abdominal pain frequency (10 ± 32 vs. 18 ± 29 (P=0.02)
- Improved stool consistency (0.2 ± 1.0 vs. 0.6 ± 1.2, P= 0.01) and frequency (0.1 ± 0.7 vs. 0.4 ± 0.7, P= 0.01)
- Overall, 34% of participants positively responded to the low FODMAP diet, which could be predicted based on higher baseline IBS-SSS scores (P=0.02)
- Participants sensitive to FODMAPs had increased pre- and postprandial ratings of gas, abdominal pain and bloating and higher exhaled methane concentrations compared to non-sensitive participants to FODMAPs
- Authors highlighted a non-significant association between FODMAP sensitivity and GI symptoms during the LNCT, with higher visceral hypersensitivity (45 ± 20, P=0.73) after ingestion of poorly absorbed and fermentable carbohydrates, with no independent predictors identified.
Conclusions
This study showed that a diet low in FODMAPs reduces GI symptoms and positively impacts bowel habits in IBS, compared with a moderate FODMAP diet.
Clinical practice applications:
- While this was a short term study, a low FODMAP diet reduced GI symptoms and affected bowel habits (more firm and less frequent stools) in IBS, compared with a diet containing moderate amounts of FODMAPs
- Knowing the above, an assessment of overall IBS severity and predominant bowel habits before the intervention may be helpful for clinicians working with younger females in their IBS management before considering a trial period with the low FOD-MAP diet as a treatment option.
Considerations for future research:
- Future trials could target a larger sample size with a more representative population, as well as assessing low FODMAP interventions over longer timeframes
- . Additionally, the assessment of biological measures such as microbiota diversity and stability, as well as metabolites (such as short chain fatty acids) could be important to understand mechanistic attributes of low FODMAP diets in IBS.
Abstract
BACKGROUND & AIMS Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS. METHODS Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively. RESULTS Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P < 0.05 for all), as well as more firm (P = 0.03) and less frequent (P < 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified. CONCLUSIONS A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www. CLINICALTRIALS gov): Registered under Clinical Trial number NCT05182593.
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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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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.
Berens, S, Dong, Y, Fritz, N, Walstab, J, D'Amato, M, Zheng, T, Wahl, V, Boekstegers, F, Bermejo, JL, Martinez, C, et al
World journal of gastroenterology. 2022;(21):2334-2349
Abstract
BACKGROUND Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
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Treatments targeting the luminal gut microbiota in patients with irritable bowel syndrome.
Algera, JP, Törnblom, H, Simrén, M
Current opinion in pharmacology. 2022;:102284
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Abstract
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 4% of the world's population. Patients with IBS experience chronic or recurrent abdominal pain in combination with altered bowel habits (diarrhea and/or constipation), and have reduced quality of life. Despite the high prevalence and substantial burden of IBS, its pathophysiology is incompletely understood and remains to be elucidated. The importance of the gut microenvironment has been highlighted in IBS, as there are signs that the gut microbiota of patients differs from healthy controls. Recent studies have aimed to alter the gut microbiota and thereby, attempted to alleviate gastrointestinal symptoms in IBS patients. We highlighted recent advances in common treatments that are targeting the luminal gut microbiota in IBS.