Probiotics as a novel approach to modulate incretins, insulin secretion and risk factors of type 2 diabetes and complications

Institut für Ernährungs- und Lebensmittelwissenschaften (IEL) an der Landwirtschaftlichen Fakultät der Rheinischen Friedrich-Wilhelm-Universität Bonn Probiotics as a novel approach to modulate incretins, insulin secretion and risk factors of type diabetes and complications Inaugural-Dissertation zur Erlangung des Grades Doktor der Ernährungs- und Lebensmittelwissenschaft (Dr oec troph.) der Landwirtschaftlichen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn von Marie-Christine Simon aus Ratingen Referent: Korreferent: Tag der mündlichen Prüfung: Erscheinungsjahr: Prof Dr rer nat Peter Stehle Prof Dr med Nanette Cathrin Schloot 13.12.2013 2014 Das Staunen ist der Anfang der Erkenntnis Platon (ca 427 v.Chr - 347 v.Chr.) Summary Background and Aim: Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents We hypothesized that daily intake of Lactobacillus (L.) reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of glucagon-like peptide (GLP-1, GLP-2) release Material and Methods: A prospective, double-blind, randomized trial was performed in 21 glucose tolerant humans (10 obese; age 51±2 years, BMI 36.0±4.8 kg/m2; 11 lean; 49±4 years, BMI 23.6±1.9 kg/m2) Participants ingested 1010 L reuteri or placebo b.i.d over weeks Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess GLP-1, GLP-2 and C-peptide secretion, hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose to measure peripheral insulin sensitivity (M-value) and endogenous glucose production (EGP) Muscle and hepatic lipid contents were measured by 1H magnetic resonance spectroscopy Immune status was assessed by measuring systemic cytokines, high-sensitive C-reactive protein (hsCRP) and lipopolysaccharide (LPS) concentrations Results: Intervention did not affect body mass, ectopic fat content and circulating cytokines M was 37% lower (p