Synbiotics and Low Grade Inflammation in Obese Subjects

Impact of the Administration of a Synbiotic on Low Grade Inflammation in Obese Subjects

The purpose of this study is to determine whether the daily administration of a synbiotic (oligofructose and Bifidobacterium animalis subsp. lactis Bb12) for six weeks contributes to improve the glucose tolerance and the low grade inflammation (as reflected as the plasmatic concentrations of ultrasensitive CRP, IL-6, sCD14 and LPS-binding protein) in obese subjects.

Study Overview

• Status: Unknown
• Conditions: Obesity; Metabolic Syndrome; Insulin Resistance; Diabetes Mellitus Type-2
• Intervention / Treatment: Dietary supplement: Synbiotic; Dietary supplement: Placebo

Detailed Description

Obesity is associated with a spectrum of metabolic disorders including high blood pressure, dyslipidemia, insulin resistance and a state of low grade inflammation that predispose individuals to the development of type-2 diabetes mellitus and cardiovascular diseases. The intestinal microbiota has been recently proposed as a new actor in the development of obesity and its complications. In animal models, high-fat diets have been shown to affect the intestinal microbiota, increasing colonic gram-negative bacteria and lipopolysaccharide (LPS) concentrations, resulting in an impaired gastrointestinal barrier function and in subsequent endotoxinemia in the animals. This phenomenon would trigger chronic inflammatory and metabolic disorders leading to insulin resistance and other complication such as hepatic steatosis. Probiotics and prebiotics are GRAS (Generally recognized as safe) food ingredients which have been proposed to maintain the balance of the intestinal microbiota. Studies in mice fed a high fat diet have shown that the administration of oligofructose increases the counts of Bifidobacterium spp. in the colon and correlatively induced decreases of the endotoxinemia and low-grade inflammation while at the same time improving insulin sensitivity.

On the basis of these antecedents, the aim of this study is to determine whether the intake of a synbiotic product (B. animalis subsp. lactis BB12+ Oligofructose) for six weeks contributes to improve the low grade inflammation and glucose tolerance of obese subjects.

Obese subjects will be randomized into two groups (Synbiotic or Placebo) stratifying by sex and age. Anthropometric data (body composition by Bod-pod, weight, height, waist circumference) and systolic and diastolic blood pressure will be registered. A food survey will be carried out by a trained dietitian to quantify fat consumption. Each subject of the Synbiotic group must ingest one gram of BB12 (containing 1010 CFU) and 5 g of oligofructose twice a day for 6 weeks while those from the Control group will receive the corresponding placebo (maltodextrin). Digestive symptoms as well as stool frequency and consistency will be registered daily during the study using ad hoc forms and the Bristol Chart.

Blood samples will be obtained at baseline, at the end of the six weeks period and one month after the end of the treatment, to determine lipid profiles and ultrasensitive C-reactive protein (CRP); plasmatic biomarkers of inflammation including IL-6, LPS binding protein and sCD14 will be also determined by Elisa using commercial kits. At the same times, a glycemia /insulinemia curve will be performed in the fasted subjects, as well as an intestinal permeability test (lactulose/mannitol/sucralose) to assess their gut barrier function. A fresh stool sample will be also obtained to characterize some bacterial population of their IM (Bifidobacterium, Lactobacillus, F. prausnitzii, Bacteroides and Clostridium cluster) by real-time PCR.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Gotteland, PhD; Phone Number: 56-2-9781471; Email: mgottela@inta.cl

Study Locations

• Chile
  • Santiago, Chile
    • Recruiting
    • Institute of Nutrition and Food Technology (INTA), University of Chile
    • Principal Investigator: Martin Gotteland, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI > 30
• Non-smokers

Exclusion Criteria:

• Current digestive diseases or antecedents of chronic digestive diseases and/or malabsorption (celiac disease, Inflammatory bowel diseases, gastroduodenal ulcers, digestive malignancies, etc)
• Use of drugs that could interfere with the intestinal microbiota or with the integrity of the gut barrier function (antibiotics, anti-inflammatory drugs, laxatives, prokinetics, etc.) during the three weeks preceding the start the study
• Treatments (medication or nutritional program) affecting body weight or glucose control
• Basal glycemia>130mg/dl (evaluated with glucose-meter)
• Immunodeficiencies (HIV, chemotherapy, radiotherapy, organ transplant).
• Current participation or recent previous having participation in another clinical trial.
• Pregnant or breastfeeding women.
• Consumption of probiotic products
• Drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synbiotic; Dietary Supplement: Synbiotic: combination of the prebiotic "Oligofructose" with the probiotic "Bifidobacterium animalis subsp. lactis Bb12"	Dietary supplement: Synbiotic; 5g of the prebiotic "Oligofructose" + 1 g of the probiotic "Bifidobacterium animalis subsp. lactis Bb12" (4x10^10 CFU/g), twice a day, for 6 weeks.
Placebo Comparator: Placebo; Dietary supplement: placebo: maltodextrin	Dietary supplement: Placebo; 6g of maltodextrin, twice a day for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasmatic Interleukin-6 (IL-6)	Plasmatic IL-6 will be determined after 6 weeks of administration of the synbiotic and compared with the IL-6 values at baseline.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasmatic LPS-binding protein	Plasmatic LPS-binding protein (LBP) will be determined after 6 weeks of administration of the synbiotic and compared with the LBP values at baseline.	6 weeks
Plasmatic sCD14	Plasmatic sCD14 will be determined after 6 weeks of administration of the synbiotic and compared with the sCD14 values at baseline.	6 weeks
glucose tolerance curve	Glucose tolerance will be determined after 6 weeks of administration of the synbiotic and compared with glucose tolerance at baseline.	6 weeks
Lipid profile	Lipid profile will be determined after 6 weeks of administration of the synbiotic and compared with the lipid profile at baseline.	6 weeks
plasmatic ultrasensitive C-Reactive Protein	Plasmatic ultrasensitive CRP will be determined after 6 weeks of administration of the synbiotic and compared with the usCRP values at baseline.	6 weeks
Plasmatic IL-6	Plasmatic IL-6 will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks
Plasmatic LBP	Plasmatic LBP will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks
Plasmatic sCD14	Plasmatic sCD14 will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks
Glucose tolerance curve	Glucose tolerance curves will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks
Lipid profile	Lipid profile will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks
Plasmatic usCRP	Plasmatic usCRP will be determined after a 1-month washout period without synbiotic administration (week 10)and compared with the baseline and post-treatment (6 weeks) values.	10 weeks

Collaborators and Investigators

• Sponsor: University of Chile

Publications and helpful links

General Publications

• Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3. doi: 10.1038/4441022a.
• Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008 Jun;57(6):1470-81. doi: 10.2337/db07-1403. Epub 2008 Feb 27.
• Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007 Nov;50(11):2374-83. doi: 10.1007/s00125-007-0791-0. Epub 2007 Sep 6.
• Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431-3. doi: 10.1126/science.1698311.
• Brunser O, Figueroa G, Gotteland M, Haschke-Becher E, Magliola C, Rochat F, Cruchet S, Palframan R, Gibson G, Chauffard F, Haschke F. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Asia Pac J Clin Nutr. 2006;15(3):368-76.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): January 1, 2011

Study Registration Dates

• First Submitted: November 1, 2010
• First Submitted That Met QC Criteria: November 4, 2010
• First Posted (Estimate): November 5, 2010

Study Record Updates

• Last Update Posted (Estimate): December 17, 2010
• Last Update Submitted That Met QC Criteria: December 16, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Obesity; Metabolic syndrome; Insulin resistance; probiotic; Prebiotic; sCD14; Lipopolysaccharide; Synbiotic; Low grade inflammation; Type-2 Diabetes; Metabolic endotoxinemia; LPS-binding protein; Oligofructose; Bifidobacterium animalis subsp. lactis Bb12
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Inflammation; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: Fondecyt-1080519