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Cited by 253Probiotics and Fermented FoodsGut microbiota and healthDiabetes Treatment and Management

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

Simon, Marie-Christine, Strassburger, Klaus, Nowotny, Bettina, Kolb, Hubert, Nowotny, Peter, Burkart, Volker, Zivehe, Fariba, Hwang, Jong-Hee +11 more·2015·Diabetes Care
DOI 10.2337/dc14-2690
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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.

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  • Certain Lactobacillus strains stimulate GLP-1 production both in vitro and in vivo.

    “Certain Lactobacillus strains were capable of stimulating GLP-1 production both in vitro and in vivo (Balakumar et al., 2018;Panwar et al., 2016;Simon et al., 2015).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Simon et al., 2015

  • In glucose-tolerant volunteers, the daily administration of Lactobacillus reuteri or the commercially available VSL#3 increased GLP-1 release into the blood, without a change in insulin sensitivity or body fat distribution.

    “The result was observed in glucose-tolerant volunteers, where the daily administration of Lactobacillus reuteri or the commercially available VSL#3 (a formulation with 8 strains of commensal bacteria, including different strains of Bifidobacterium and Lactobacillus) increased GLP-1 release into the blood, without a change in insulin sensitivity or body fat distribution [120, 124].”

    From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [124]

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Authors
Simon, M.-C., Strassburger, K., Nowotny, B., Kolb, H., Nowotny, P., Burkart, V., Zivehe, F., Hwang, J.-H., Stehle, P., Pacini, G., Hartmann, B., Holst, J. J., MacKenzie, C., Bindels, L. B., Martinez, I., Walter, J., Henrich, B., Schloot, N. C., & Roden, M.
Affiliations
  • Deutsches Diabetes-Zentrum e.V. (DE)
  • Verbund Katholischer Kliniken Düsseldorf (DE)
  • Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany
  • University of Bonn (DE)
  • National Research Council (IT)
  • University of Copenhagen (DK)
  • Heinrich Heine University Düsseldorf (DE)
  • University of Nebraska–Lincoln (US)
  • Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE
Corresponding author
  • Schloot, Nanette C.
  • Roden, Michael
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2015-06-17
Volume
38
Issue
10
Pages
1827-1834
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc14-2690
OpenAlex
W2133474627
Cited by
253
References
42
Citations by year
2026: 13 · 2025: 22 · 2024: 24 · 2023: 33 · 2022: 32 · 2021: 30 · 2020: 21 · 2019: 23 · 2018: 22 · 2017: 15 · 2016: 17 · 2015: 1
FWCI
24.54
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Libraries (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
Sanofi
Topics
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
Lactobacillus reuteri, probiotics, incretin secretion, glucagon-like peptide-1, glucagon-like peptide-2, insulin secretion, insulin sensitivity, gut microbiota, glucose tolerance, obesity, C-peptide, endogenous glucose production, cytokines, endotoxin
MeSH terms
Insulin Secretion, Adult, Aged, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glucagon, Glucose, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Pilot Projects, Prospective Studies, Protein Precursors, Glucose Clamp Technique, Oxidative Stress, Probiotics, Insulin-Secreting Cells, Limosilactobacillus reuteri, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2, Incretins

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