Intake of <i>Lactobacillus reuteri</i> Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept

  • Marie-Christine Simon
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Klaus Strassburger
    German Center for Diabetes Research, Düsseldorf, Germany
  • Bettina Nowotny
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Hubert Kolb
    West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany
  • Peter Nowotny
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Volker Burkart
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Fariba Zivehe
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Jong-Hee Hwang
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Peter Stehle
    Department of Nutrition and Food Science, Nutritional Physiology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
  • Giovanni Pacini
    Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy
  • Bolette Hartmann
    Novo Nordisk Foundation Center for Basic Metabolic Research, Department for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Jens J. Holst
    Novo Nordisk Foundation Center for Basic Metabolic Research, Department for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Colin MacKenzie
    Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany
  • Laure B. Bindels
    Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE
  • Ines Martinez
    Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE
  • Jens Walter
    Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE
  • Birgit Henrich
    Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany
  • Nanette C. Schloot
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • Michael Roden
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany

抄録

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>A prospective, double-blind, randomized trial was performed in 21 glucose-tolerant humans (11 lean: age 49 ± 7 years, BMI 23.6 ± 1.7 kg/m2; 10 obese: age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m2). Participants ingested 1010 b.i.d. L. reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-2H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by 1H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P &lt; 0.01) and 43% (P &lt; 0.01), respectively, compared with placebo, along with 49% higher insulin (P &lt; 0.05) and 55% higher C-peptide secretion (P &lt; 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release.</jats:p> </jats:sec>

収録刊行物

  • Diabetes Care

    Diabetes Care 38 (10), 1827-1834, 2015-06-17

    American Diabetes Association

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