{
  "abstract": "Background Food additives have been linked to increased Crohn’s disease (CD) risk and activity, but their human quantification has not been explored.Objective We aimed to measure artificial sweeteners and emulsifier polysorbate-80 (P-80) in patients with CD and assess their associations with disease activity.Design 1461 biosamples from 487 subjects (245 CD and 242 controls) across Australia, Hong Kong and Chinese Mainland were analysed for aspartame, sucralose, saccharin and P-80 levels in stool, urine and serum. CD activity was assessed using Crohn’s Disease Activity Index and faecal calprotectin. A generalised linear model (GLM) with P-80 and sweeteners distinguished active CD from inactive CD.Results Patients with CD had higher sweetener levels compared with controls across cohorts (all p<0.0001). P-80 underwent predominantly hydrolytic and oxidoreductive degradation in CD and controls, respectively, while its native form was undetectable. CD-associated P-80 metabolites positively correlated with urinary sweeteners in patients with CD. In vitro, CD-associated P-80 metabolites increased gut permeability, enabling translocation of sweeteners across the epithelium. Sweeteners and specific CD-associated P-80 metabolites were higher in active CD. The GLM built using sweeteners and P-80 metabolites distinguished active CD from inactive CD, achieving an area under the curve (AUC) of 0.86 in the discovery cohort and average AUC of 0.94 in two independent validation cohorts from Australia and Chinese Mainland.Conclusion This is the first human study to demonstrate distinct P-80 metabolism in patients with CD compared with controls. Dietary sweeteners and P-80 metabolites showed significant correlations with disease activity, suggesting their potential utility as non-invasive biomarkers for CD activity assessment.",
  "authors": [
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Jingwan Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi, China"
      ],
      "name": "Jielun Hu"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Xinyi Tang"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Yanjiao Ruan"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Fangjia Hao"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Wenqing Zhang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia",
        "Department of Sport, Exercise and Nutrition Sciences, La Trobe University, Melbourne, Victoria, Australia"
      ],
      "name": "Gina Trakman"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia",
        "Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"
      ],
      "name": "Amy L Hamilton"
    },
    {
      "affiliations": [
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Winnie Lin"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"
      ],
      "name": "Yang Sun"
    },
    {
      "affiliations": [
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Jessica Y L Ching"
    },
    {
      "affiliations": [
        "Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Jing Jie Teh"
    },
    {
      "affiliations": [
        "Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia",
        "Graduate School of International Agricultural Technology, Institute of Green Bio Science and Technology, Seoul National University, Seoul, Korea (the Republic of)"
      ],
      "name": "Seungha Kang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia",
        "Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"
      ],
      "name": "Amy Wilson-O’ Brien"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia"
      ],
      "name": "Annalise Stanley"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Department of Anaesthesia and Intensive Care, Falcuty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Lin Zhang"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Joseph J Y Sung"
    },
    {
      "affiliations": [
        "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China",
        "Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Jun Yu"
    },
    {
      "affiliations": [
        "Division of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"
      ],
      "name": "Yinglei Miao"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "Center for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Francis K L Chan"
    },
    {
      "affiliations": [
        "Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia",
        "Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia"
      ],
      "name": "Mark Morrison"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia",
        "Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"
      ],
      "name": "Michael Kamm"
    },
    {
      "affiliations": [
        "Microbiota I-Center (MagIC), Hong Kong SAR, China",
        "New Cornerstone Science Laboratory, The Chinese University of Hong Kong, Hong Kong SAR, China"
      ],
      "name": "Siew C Ng"
    }
  ],
  "title": "Quantifying artificial sweeteners and emulsifiers in Crohn’s disease and its relationship with disease activity: the ENIGMA study – a novel and targeted approach",
  "uid": "80adae1c-9261-51ab-a1f0-37a5e238f1f1"
}