Gastroenterology

Gastroenterology

Volume 153, Issue 4, October 2017, Pages 936-947
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial

https://doi.org/10.1053/j.gastro.2017.06.010Get rights and content

Background & Aims

Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS.

Methods

We performed a 2×2 factorial trial of 104 patients with IBS (18–65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks.

Results

There was no significant interaction between the interventions in adequate relief of symptoms (P = .52) or Bifidobacterium species (P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples.

Conclusions

In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221.

Section snippets

Study Design and Participants

We performed a 2×2 factorial design, multicenter, randomized, placebo-controlled trial from clinics at 2 hospitals in London, UK. Patients aged 18–65 years of age with diarrhea-predominant (IBS-D), mixed subtype (IBS-M), or unsubtyped irritable bowel syndrome (IBS-U), according to Rome III were recruited. Major medical conditions such as inflammatory bowel disease and diabetes were excluded, and coeliac disease was excluded by evaluation of endomysial IgA, tissue transglutaminase IgA serology,

Results

Patients were recruited between January 28, 2013 and November 21, 2014. A total of 162 patients were screened of whom 58 were ineligible. Therefore, 104 patients were randomized to the sham (n=53) or low FODMAP diet (n=51) and placebo (n=51) or probiotic (n=53) as follows: sham/placebo (n=27), sham/probiotic (n=26), low FODMAP diet/placebo (n=24), and low FODMAP diet /probiotic (n=27) (Figure 1). Nine patients were withdrawn from the trial (6 commenced antibiotics [2 sham, 4 low FODMAP diet], 1

Discussion

This RCT demonstrates that low FODMAP dietary advice leads to adequate relief of GI symptoms in 57% of patients compared with 38% of patients receiving sham dietary advice (and 61% and 39% in the per protocol analysis). Although this finding did not reach statistical significance, the totality of the clinical outcomes reported here point toward the clinical effectiveness of the low FODMAP diet over and above placebo, the first to do so using dietary advice, making it directly relevant to

Acknowledgments

The authors thank Penny Neild and Rani Nagarajah for assistance with patient recruitment and Rob Grant for statistical advice. We also thank Monash University, Melbourne, Australia, for access to their FODMAP food composition database for analysis of FODMAP intake.

The research was performed at King’s College London, Guy’s and St Thomas’ NHS Foundation Trust, and samples were also analyzed at the Rowett Institute and the Fondazione Edmund Mach.

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    Conflict of interest H.S. reports non-financial support from CD Investments VSL Pharmaceuticals; M.C.L. has developed a mobile app with Food Maestro. F.M.F. and P.L. received grants from Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). K.W. has developed a mobile app with Food Maestro, received personal fees from Danone, research grant from Clasado. F.F., E.F., M.S., K.T., J.O.L., P.M.I. have nothing to disclose.

    The National Institute for Health Research funded the study and had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript. F.M.F. and P.L. receive financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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