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Diabetes Care. 2015 Oct;38(10):1827-34. doi: 10.2337/dc14-2690. Epub 2015 Jun 17.

Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept.

Author information

1
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
2
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.
3
West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany.
4
Department of Nutrition and Food Science, Nutritional Physiology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
5
Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy.
6
Novo Nordisk Foundation Center for Basic Metabolic Research, Department for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
7
Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine University, Düsseldorf, Germany.
8
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE.
9
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.
10
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.
11
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.

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.

RESEARCH DESIGN AND 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01250106.

Comment in

PMID:
26084343
DOI:
10.2337/dc14-2690
[Indexed for MEDLINE]

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