{
  "abstract": "Background Insulin-like peptide 5 (INSL5) is an enteroendocrine hormone expressed in distal colonic ‘L cells’. Bile acid receptor agonists are known to stimulate INSL5 secretion in primary cell culture, and administration of an INSL5 analogue in animals promotes colonic motility.Objective This study used a new immunoassay to measure INSL5 in human blood samples, enabling assessment of whether rectal bile acids stimulate INSL5 release in humans and whether INSL5 levels are altered in patients with chronic diarrhoea.Design Serum/plasma samples from previously performed studies were used, including healthy volunteers (n=7) who received a rectal enema of taurocholic acid (TCA); fasting and post prandial samples from healthy volunteers (n=10); patients with bile acid diarrhoea (BAD) (n=19) or irritable bowel syndrome with diarrhoea (IBS-D) (n=8); and patients with IBS-D (n=64) treated with ondansetron or placebo.Results Rectal TCA but not a control enema promptly elevated plasma INSL5, with the increase in INSL5 correlating negatively with time to, and positively with desire to, defecate post enema. Healthy volunteers had low INSL5 levels (<100 pg/mL), with no change following a mixed meal. Patients with BAD had elevated INSL5 levels, with average stool consistency being positively correlated with serum INSL5 (p<0.001). In people with IBS-D, INSL5 was elevated (>100 pg/mL) in 42%, and this subgroup showed greater improvements in stool consistency with ondansetron therapy (p<0.05).Conclusion The study highlights that rectal bile acids stimulate INSL5 secretion in humans, and that INSL5 levels are associated with a colonic pro-motility response and pathophysiology of chronic diarrhoea.",
  "authors": [
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Christopher A Bannon"
    },
    {
      "affiliations": [
        "Division of Digestive Diseases, Imperial College London, London, UK",
        "Imperial College Healthcare Trust, London, UK"
      ],
      "name": "Julian R F Walters"
    },
    {
      "affiliations": [
        "Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia"
      ],
      "name": "Tongzhi Wu"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Richard G Kay"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Austin Punnoose"
    },
    {
      "affiliations": [
        "Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK",
        "NIHR Nottingham Biomedical Research Centre, Nottingham, UK"
      ],
      "name": "Robin C Spiller"
    },
    {
      "affiliations": [
        "Eli Lilly and Company, Indianapolis, Indiana, USA"
      ],
      "name": "Jonathan Wilson"
    },
    {
      "affiliations": [
        "Eli Lilly and Company, Lilly Biotechnology Center, San Diego, California, USA"
      ],
      "name": "Petra Verdino"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Peter Barker"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Keith Burling"
    },
    {
      "affiliations": [
        "Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia"
      ],
      "name": "Michael Horowitz"
    },
    {
      "affiliations": [
        "Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia"
      ],
      "name": "Christopher K Rayner"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK",
        "Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK"
      ],
      "name": "Alexander C Ford"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Frank Reimann"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science, Cambridge, UK"
      ],
      "name": "Fiona M Gribble"
    }
  ],
  "title": "Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea",
  "uid": "59ebb0f5-255c-562c-8e9e-dfc557f1e001"
}