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Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome

  • Author Footnotes
    a Authors share co-first authorship.
    Megan Rossi
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    a Authors share co-first authorship.
    Affiliations
    Department of Nutritional Sciences, King’s College London, London, United Kingdom

    Guy’s and St Thomas’ NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom
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    a Authors share co-first authorship.
    Raphael Aggio
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    Affiliations
    Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
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  • Heidi M. Staudacher
    Affiliations
    Department of Nutritional Sciences, King’s College London, London, United Kingdom

    Guy’s and St Thomas’ NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom
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  • Miranda C. Lomer
    Affiliations
    Department of Nutritional Sciences, King’s College London, London, United Kingdom

    Guy’s and St Thomas’ NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom
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  • James O. Lindsay
    Affiliations
    Bart’s Health NHS Trust, Department of Gastroenterology, United Kingdom, and Barts and the London School of Medicine, Blizard Institute, Queen Mary University of London, London, United Kingdom
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  • Peter Irving
    Affiliations
    Department of Nutritional Sciences, King’s College London, London, United Kingdom

    Guy’s and St Thomas’ NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom
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    a Authors share co-first authorship.
    Chris Probert
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    Affiliations
    Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
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    a Authors share co-first authorship.
    Kevin Whelan
    Correspondence
    Reprint requests Address requests for reprints to: Kevin Whelan, Department of Nutritional Sciences, King’s College London, London, United Kingdom SE1 9NH.
    Footnotes
    a Authors share co-first authorship.
    Affiliations
    Department of Nutritional Sciences, King’s College London, London, United Kingdom
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  • Author Footnotes
    a Authors share co-first authorship.
Published:October 06, 2017DOI:https://doi.org/10.1016/j.cgh.2017.09.055

      Background & Aims

      Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS.

      Methods

      Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation.

      Results

      Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%–99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%–92%). End of treatment models achieved similar predictive powers and accuracies.

      Conclusion

      Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221.

      Keywords

      Abbreviations used in this paper:

      FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), GC-MS (gas chromatography–mass spectrometry), IBS (irritable bowel syndrome), IBS-D (diarrhea-predominant irritable bowel syndrome), IBS-M (mixed subtype irritable bowel syndrome), IBS-SSS (Irritable Bowel Syndrome Symptom Scoring System), IBS-U (unsubtyped irritable bowel syndrome), LFD (low-FODMAP diet), PCA (principal component analysis), PLS (partial least squares), VOC (volatile organic compound)
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      References

        • Lovell R.M.
        • Ford A.C.
        Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis.
        Clin Gastroenterol Hepatol. 2012; 10: 712-721 e714
        • Maxion-Bergemann S.
        • Thielecke F.
        • Abel F.
        • et al.
        Costs of irritable bowel syndrome in the UK and US.
        Pharmacoeconomics. 2006; 24: 21-37
        • Rajilic-Stojanovic M.
        • Jonkers D.M.
        • Salonen A.
        • et al.
        Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?.
        Am J Gastroenterol. 2015; 110: 278-287
        • Pozuelo M.
        • Panda S.
        • Santiago A.
        • et al.
        Reduction of butyrate- and methane-producing microorganisms in patients with irritable bowel syndrome.
        Sci Rep. 2015; 5: 12693
        • Crouzet L.
        • Gaultier E.
        • Del'Homme C.
        • et al.
        The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota.
        Neurogastroenterol Motil. 2013; 25: e272-e282
        • Tap J.
        • Derrien M.
        • Tornblom H.
        • et al.
        Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome.
        Gastroenterology. 2017; 152: 111-123 e118
        • Collins S.M.
        A role for the gut microbiota in IBS.
        Nat Rev Gastroenterol Hepatol. 2014; 11: 497-505
        • Muegge B.D.
        • Kuczynski J.
        • Knights D.
        • et al.
        Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans.
        Science. 2011; 332: 970-974
        • Aggio R.B.
        • White P.
        • Jayasena H.
        • et al.
        Irritable bowel syndrome and active inflammatory bowel disease diagnosed by faecal gas analysis.
        Aliment Pharmacol Ther. 2017; 45: 82-90
        • Ahmed I.
        • Greenwood R.
        • Costello Bde L.
        • et al.
        An investigation of fecal volatile organic metabolites in irritable bowel syndrome.
        PLoS One. 2013; 8: e58204
        • Staudacher H.
        • Whelan K.
        The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in irritable bowel syndrome.
        Gut. 2017; 66: 1517-1527
        • Marsh A.
        • Eslick E.M.
        • Eslick G.D.
        Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? a comprehensive systematic review and meta-analysis.
        Eur J Nutr. 2016; 55: 897-906
        • Staudacher H.M.
        • Irving P.M.
        • Lomer M.C.
        • et al.
        Mechanisms and efficacy of dietary FODMAP restriction in IBS.
        Nat Rev Gastroenterol Hepatol. 2014; 11: 256-266
        • McKenzie Y.A.
        • Thompson J.
        • Gulia P.
        • et al.
        British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update).
        J Hum Nutr Diet. 2016; 29: 576-592
        • Celis-Morales C.
        • Livingstone K.M.
        • Marsaux C.F.
        • et al.
        Effect of personalized nutrition on health-related behaviour change: evidence from the Food4Me European randomized controlled trial.
        Int J Epidemiol. 2017; 46: 578-588
        • Staudacher H.M.
        • Lomer M.C.E.
        • Farquharson F.M.
        • et al.
        Diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and probiotic restores Bifidobacterium species: a randomized controlled trial.
        Gastroenterology. 2017; 153: 936-947
        • Francis C.Y.
        • Morris J.
        • Whorwell P.J.
        The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.
        Aliment Pharmacol Ther. 1997; 11: 395-402
        • Aggio R.B.
        • de Lacy Costello B.
        • White P.
        • et al.
        The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies.
        J Breath Res. 2016; 10: 017106
        • Shepherd S.F.
        • McGuire N.D.
        • de Lacy Costello B.P.
        • et al.
        The use of a gas chromatograph coupled to a metal oxide sensor for rapid assessment of stool samples from irritable bowel syndrome and inflammatory bowel disease patients.
        J Breath Res. 2014; 8: 026001
        • Delen D.
        Analysis of cancer data: a data mining approach.
        Expert Systems. 2009; 26: 100-112
      1. R: a language and environment for statistical computing [computer program]. R Foundation for Statistical Computing, Vienna, Austria2015
        • Chumpitazi B.P.
        • Cope J.L.
        • Hollister E.B.
        • et al.
        Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome.
        Aliment Pharmacol Ther. 2015; 42: 418-427
        • Bohn L.
        • Storsrud S.
        • Liljebo T.
        • et al.
        Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial.
        Gastroenterology. 2015; 149: 1399-1407 e1392
        • Bennet S.M.P.
        • Bohn L.
        • Storsrud S.
        • et al.
        Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs.
        Gut. 2017; 0: 1-10
        • Wilder-Smith C.H.
        • Olesen S.S.
        • Materna A.
        • et al.
        Predictors of response to a low-FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance.
        Aliment Pharmacol Ther. 2017; 45: 1094-1106
        • Dimidi E.
        • Rossi M.
        • Whelan K.
        Irritable bowel syndrome and diet: where are we in 2018?.
        Curr Opin Clin Nutr Metab Care. 2017; 20: 456-463
        • Garner C.E.
        • Smith S.
        • de Lacy Costello B.
        • et al.
        Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease.
        FASEB J. 2007; 21: 1675-1688
        • Walton C.
        • Montoya M.P.
        • Fowler D.P.
        • et al.
        Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn's disease: an observational study.
        Eur J Clin Nutr. 2016; 70: 1052-1056
        • Hustoft T.N.
        • Hausken T.
        • Ystad S.O.
        • et al.
        Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome.
        Neurogastroenterol Motil. 2017; 29
        • Jeffery I.B.
        • O'Toole P.W.
        • Ohman L.
        • et al.
        An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.
        Gut. 2012; 61: 997-1006

      References

        • Staudacher H.
        • Whelan K.
        The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in irritable bowel syndrome.
        Gut. 2017; 66: 1517-1527
        • Staudacher H.M.
        • Irving P.M.
        • Lomer M.C.E.
        • et al.
        The challenges of control groups, placebos and blinding in clinical trials of dietary interventions.
        Proceedings of the Nutrition Society. 2017; 76: 203-212
        • Shepherd S.J.
        • Gibson P.R.
        Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management.
        J Am Diet Assoc. 2006; 106: 1631-1639
        • Francis C.Y.
        • Morris J.
        • Whorwell P.J.
        The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.
        Aliment Pharmacol Ther. 1997; 11: 395-402
        • Staudacher H.M.
        • Lomer M.C.E.
        • Farquharson F.M.
        • et al.
        Diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and probiotic restores Bifidobacterium species: a randomized controlled trial.
        Gastroenterology. 2017; 153: 936-947