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

Marie-Christine Simon; Klaus Strassburger; Bettina Nowotny; Hubert Kolb; Peter Nowotny; Volker Burkart; Fariba Zivehe; Jong-Hee Hwang; Peter Stehle; Giovanni Pacini; Bolette Hartmann; Jens J Holst; Colin MacKenzie; Laure B Bindels; Ines Martinez; Jens Walter; Birgit Henrich; Nanette C Schloot; Michael Roden

doi:10.2337/dc14-2690

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

Marie-Christine Simon, Klaus Strassburger, Bettina Nowotny, Hubert Kolb, Peter Nowotny, Volker Burkart, Fariba Zivehe, Jong-Hee Hwang, Peter Stehle, Giovanni Pacini, Bolette Hartmann, Jens J Holst, Colin MacKenzie, Laure B Bindels, Ines Martinez, Jens Walter, Birgit Henrich, Nanette C Schloot, Michael Roden

102 Citationer (Scopus)

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/m²; 10 obese: Age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m²). Participants ingested 10¹⁰b.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 euglycemichyperinsulinemic 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. 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 strainmay serve as a novel therapeutic approach to improve glucose-dependent insulin release.

Originalsprog	Engelsk
Tidsskrift	Diabetes Care
Vol/bind	38
Udgave nummer	10
Sider (fra-til)	1827-34
Antal sider	8
ISSN	0149-5992
DOI	https://doi.org/10.2337/dc14-2690
Status	Udgivet - okt. 2015

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Citationsformater

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. (2015). Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept. Diabetes Care, 38(10), 1827-34. https://doi.org/10.2337/dc14-2690

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, JJ, MacKenzie, C, Bindels, LB, Martinez, I, Walter, J, Henrich, B, Schloot, NC & Roden, M 2015, 'Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept', Diabetes Care, bind 38, nr. 10, s. 1827-34. https://doi.org/10.2337/dc14-2690

@article{b1b2c88576464629a7184d15c30e162b,

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. 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/m2; 10 obese: Age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m2). Participants ingested 1010b.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 euglycemichyperinsulinemic 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. 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 strainmay serve as a novel therapeutic approach to improve glucose-dependent insulin release.",

author = "Marie-Christine Simon and Klaus Strassburger and Bettina Nowotny and Hubert Kolb and Peter Nowotny and Volker Burkart and Fariba Zivehe and Jong-Hee Hwang and Peter Stehle and Giovanni Pacini and Bolette Hartmann and Holst, {Jens J} and Colin MacKenzie and Bindels, {Laure B} and Ines Martinez and Jens Walter and Birgit Henrich and Schloot, {Nanette C} and Michael Roden",

note = "{\textcopyright} 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",

year = "2015",

month = oct,

doi = "10.2337/dc14-2690",

language = "English",

volume = "38",

pages = "1827--34",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "10",

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TY - JOUR

T1 - Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans

T2 - A Proof of Concept

AU - Simon, Marie-Christine

AU - Strassburger, Klaus

AU - Nowotny, Bettina

AU - Kolb, Hubert

AU - Nowotny, Peter

AU - Burkart, Volker

AU - Zivehe, Fariba

AU - Hwang, Jong-Hee

AU - Stehle, Peter

AU - Pacini, Giovanni

AU - Hartmann, Bolette

AU - Holst, Jens J

AU - MacKenzie, Colin

AU - Bindels, Laure B

AU - Martinez, Ines

AU - Walter, Jens

AU - Henrich, Birgit

AU - Schloot, Nanette C

AU - Roden, Michael

PY - 2015/10

Y1 - 2015/10

N2 - 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/m2; 10 obese: Age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m2). Participants ingested 1010b.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 euglycemichyperinsulinemic 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. 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 strainmay serve as a novel therapeutic approach to improve glucose-dependent insulin release.

AB - 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/m2; 10 obese: Age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m2). Participants ingested 1010b.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 euglycemichyperinsulinemic 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. 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 strainmay serve as a novel therapeutic approach to improve glucose-dependent insulin release.

U2 - 10.2337/dc14-2690

DO - 10.2337/dc14-2690

M3 - Journal article

C2 - 26084343

SN - 0149-5992

VL - 38

SP - 1827

EP - 1834

JO - Diabetes Care

JF - Diabetes Care

IS - 10

ER -

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

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