title: Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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/m(2); 10 obese: age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m(2)). Participants ingested 10(10) 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-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by (1)H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays.
  
  
  RESULTS
  In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P < 0.01) and 43% (P < 0.01), respectively, compared with placebo, along with 49% higher insulin (P < 0.05) and 55% higher C-peptide secretion (P < 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Simon
authors.affiliation: German Center for Diabetes Research, Düsseldorf, Germany Institute for Biometry and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strassburger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.affiliation: West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Burkart
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Fariba
authors.initials: F
authors.lastname: Zivehe
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Nutrition and Food Science, Nutritional Physiology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Stehle
authors.affiliation: Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Department for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Department for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Colin
authors.initials: C
authors.lastname: MacKenzie
authors.affiliation: Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.
authors.forename: Laure B
authors.initials: LB
authors.lastname: Bindels
authors.affiliation: Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.
authors.forename: Ines
authors.initials: I
authors.lastname: Martinez
authors.affiliation: Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE Department of Agricultural, Nutritional and Food Science, University of Alberta, AB, Canada Department of Biological Sciences, University of Alberta, Edmonton, Canada.
authors.forename: Jens
authors.initials: J
authors.lastname: Walter
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Henrich
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de schloot@ddz.uni-duesseldorf.de.
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de schloot@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D052200:Limosilactobacillus reuteri; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010865:Pilot Projects; D019936:Probiotics / Q000494:pharmacology*; D011446:Prospective Studies; D011498:Protein Precursors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D053767:Glucagon-Like Peptide 2; D054795:Incretins; D007328:Insulin; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose