Neurogastroenterology & Motility. 2020;32:e13860. wileyonlinelibrary.com/journal/nmo | 1 of 13 https://doi.org/10.1111/nmo.13860 © 2020 John Wiley & Sons Ltd Received: 15 August 2019 | Revised: 6 March 2020 | Accepted: 30 March 2020 DOI: 10.1111/nmo.13860 ORIGINAL ARTICLE Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome Bani Ahluwalia 1,2 | Maria K. Magnusson 1 | Lena Böhn 2,3 | Stine Störsrud 3 | Fredrik Larsson 2 | Otto Savolainen 4 | Alastair Ross 4,5 | Magnus Simrén 3,6 * | Lena Öhman 1,3 * *Magnus Simrén and Lena Öhman shared senior authorship. 1 Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden 2 Calmino Group AB, Gothenburg, Sweden 3 Institute of Medicine, University of Gothenburg, Gothenburg, Sweden 4 Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden 5 Proteins and Metabolites Team, AgResearch, Lincoln, New Zealand 6 Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Correspondence Bani Ahluwalia, Department of Microbiology and Immunology, University of Gothenburg, Box 435, Gothenburg 405 30, Sweden. Email: bani.ahluwalia@gu.se Funding information This study was supported by Swedish Medical Research Council (grants 13409, 21691, 21692 and 2015-02317), AFA Insurance, and the Faculty of Medicine, University of Gothenburg and Calmino Group AB, Sweden, supported the study with treatment tablets. Abstract Background: Aloe barbadensis Mill. (Aloe) with potential prebiotic effects has been suggested to reduce symptoms in patients with irritable bowel syndrome (IBS). We therefore aimed to determine the effects of an Aloe extract on symptoms of IBS, and evaluate whether effects may be mediated by fecal microbiota and metabolites in a randomized, double-blind, controlled trial. Methods: Patient with IBS diagnosed according to the ROME III criteria (all subtypes), received Aloe or control treatment (inulin) for 4 weeks. IBS Symptom Severity Score (IBS-SSS) was assessed, and fecal samples collected before and at end of treatment. Fecal microbiota composition and metabolomic profile were determined. Key results: In total, 160 IBS patients completed the study. The overall severity of IBS symptoms was reduced in both Aloe and control treatment groups (P < .001, both groups, comparing baseline vs end of treatment), without difference between groups (P = .62). The frequency of responders (IBS-SSS reduction ≥ 50) did not differ be- tween Aloe treatment (n = 33, 39%) and control (n = 34, 45%) (P = .49). However, fecal microbiota and metabolite profiles differed between Aloe, but not control treatment responders and non-responders both before and after treatment. Conclusion: In a mixed group of IBS patients, Aloe was not superior to control treat - ment, although it showed potential to reduce IBS symptom severity in subsets of IBS patients which could be predicted by fecal microbiota and metabolite profiles. ClinicalTrials.gov no: NCT01400048. KEYWORDS Aloe, fecal metabolites, gastrointestinal microbiota, gastrointestinal symptoms, irritable bowel syndrome, prebiotic