Fermentable Carbohydrates [FODMAPs] Exacerbate Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: A Randomised, Double-blind, Placebo-controlled, Cross-over, Re-challenge Trial

Cox, Susanne; Prince, Alexis C; Myers, Camryn; Irving, Peter M; Lindsay, James O.; Lomer, Miranda; Whelan, Kevin

doi:10.1093/ecco-jcc/jjx073

Cited by 112 publications

(108 citation statements)

References 39 publications

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“…Proof‐of‐concept: Re‐challenge study in patients with IBD showed symptom induction with 3‐day fructan challenge …”

Section: Dietary Therapies For the Treatment Of Irritable Bowel Syndromementioning

confidence: 99%

“…With the high frequency of IBS symptoms in quiescent IBD, the low FODMAP diet is now being integrated into clinical practice for control of functional symptoms in IBD patients. A small body of evidence suggests similar benefits in quiescent IBD patients as seen with IBS . However, theoretical concern exists for the potential lowering of SCFA with use of the low FODMAP diet, as reduced SCFA has been implicated in increasing susceptibility to colitis in mice .…”

Section: Dietary Therapies For the Treatment Of Functional Symptoms Imentioning

confidence: 99%

“…Another study assessing the low FODMAP diet created a “sham” diet which attempted to not alter other dietary constituents . One study in quiescent IBD utilized a re‐challenge protocol to assess symptom induction rather than symptom reduction through exclusion diet . An alternative to the comparison of two dietary interventions is to compare two therapies, for example, diet and drug therapy or diet and psychological therapy .…”

Section: Future Dietary Research—optimizing Research Designmentioning

confidence: 99%

“…It is thought that symptoms should usually resolve after 3‐4 weeks on an exclusion diet, but this should be clearly defined and communicated for each dietary therapy following thorough investigation, to ensure restrictive diets are not used for longer than necessary. A re‐challenge protocol has been published for the low FODMAP diet largely based on clinical experience, and a small number of trials recently published . In IBS patients, FODMAP intake was reduced to 36% of usual intake during the restrictive phase, but increased to 79% of usual intake following re‐challenge .…”

Section: Future Dietary Research—key Research Questionsmentioning

confidence: 99%

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Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

Tuck

Vanner

2017

Neurogastroenterology Motil

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“…Proof‐of‐concept: Re‐challenge study in patients with IBD showed symptom induction with 3‐day fructan challenge …”

Section: Dietary Therapies For the Treatment Of Irritable Bowel Syndromementioning

confidence: 99%

Section: Dietary Therapies For the Treatment Of Functional Symptoms Imentioning

confidence: 99%

Section: Future Dietary Research—optimizing Research Designmentioning

confidence: 99%

Section: Future Dietary Research—key Research Questionsmentioning

confidence: 99%

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Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

Tuck

Vanner

2017

Neurogastroenterology Motil

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“…As a measure of inflammation, two studies have shown no differences in fecal calprotectin with use of the low‐FODMAP diet in IBD, although values were in a lower range that is less precise. One study showed increased fecal calprotectin following FODMAP re‐challenges (30 µg/g vs 73 µg/g, P = .02), but overall values were low as might be expected in a quiescent IBD population; hence, clinical significance is difficult to extrapolate . One randomized placebo‐controlled trial of 52 IBD patients with quiescent disease found no difference in inflammatory markers including fecal calprotectin and circulating α4β7 + blood T cells after a low‐FODMAP diet .…”

Section: Introductionmentioning

confidence: 99%

The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome

Tuck

Caminero

Vargas

et al. 2019

Neurogastroenterology Motil

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Background A low fermentable carbohydrate (FODMAP) diet is used in quiescent inflammatory bowel disease when irritable bowel syndrome‐like symptoms occur. There is concern that the diet could exacerbate inflammation by modifying microbiota and short‐chain fatty acid (SCFA) production. We examined the effect of altering dietary FODMAP content on inflammation in preclinical inflammatory models. Methods C57BL/6 mice were given 3% dextran sodium sulfate (DSS) in drinking water for 5 days and recovered for 3 weeks (postinflammatory, n = 12), or 5 days (positive‐control, n = 12). Following recovery, DSS‐treated or control mice (negative‐control, n = 12) were randomized to 2‐week low‐ (0.51 g/100 g total FODMAP) or high‐FODMAP (4.10 g) diets. Diets mimicked human consumption containing fructose, sorbitol, galacto‐oligosaccharide, and fructan. Colons were assessed for myeloperoxidase (MPO) activity and histological damage. Supernatants were generated for perforated patch‐clamp recordings and cytokine measurement. Cecum contents were analyzed for microbiota, SCFA, and branched‐chain fatty acids (BCFA). Data were analyzed by two‐way ANOVA with Bonferroni. Key results Inflammatory markers were higher in the positive‐control compared with negative‐control and postinflammatory groups, but no differences occurred between the two diets within each treatment (MPO P > .99, histological scores P > .99, cytokines P > .05), or the perforated patch‐clamp recordings (P > .05). Microbiota clustered mainly based on DSS exposure. No difference in SCFA content occurred. Higher total BCFA occurred with the low‐FODMAP diet in positive‐control (P < .01) and postinflammatory groups (P < .01). Conclusions and inferences In this preclinical study, reducing dietary FODMAPs did not exacerbate nor mitigate inflammation. Microbiota profile changes were largely driven by inflammation rather than diet. Low FODMAP intake caused a shift toward proteolytic fermentation following inflammation.

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Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production

Tian,

Paudel,

Hao

et al. 2023

Cancer Reports

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Background and AimThere is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis.MethodsFour‐week‐old wild‐type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis‐associated colorectal cancer (CRC) was initiated with three 7‐day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development.ResultsMice consuming inulin‐containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS‐treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin‐fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin‐fed but not in the control group during the DSS cycle. Consequently, the remaining inulin‐fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin‐fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin‐fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis.ConclusionsOur study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.

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Fermentable Carbohydrates [FODMAPs] Exacerbate Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: A Randomised, Double-blind, Placebo-controlled, Cross-over, Re-challenge Trial

Abstract: At the relatively high doses used, fructans, but not GOS or sorbitol, exacerbated FGS in quiescent IBD. Further research is required to determine whether a low FODMAP diet reduces FGS in IBD and the degree of FODMAP restriction required for symptom improvement.

Cited by 112 publications

References 39 publications

Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome

Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production

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