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Synbiotics and Low Grade Inflammation in Obese Subjects

U

University of Chile

Status

Unknown

Conditions

Diabetes Mellitus Type-2
Insulin Resistance
Obesity
Metabolic Syndrome

Treatments

Dietary Supplement: Synbiotic
Dietary Supplement: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT01235026
Fondecyt-1080519

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 estimated patients

Sex

All

Ages

20 to 50 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

44 participants in 2 patient groups, including a placebo group

Synbiotic
Experimental group
Description:
Dietary Supplement: Synbiotic: combination of the prebiotic "Oligofructose" with the probiotic "Bifidobacterium animalis subsp. lactis Bb12"
Treatment:
Dietary Supplement: Synbiotic
Placebo
Placebo Comparator group
Description:
Dietary supplement: placebo: maltodextrin
Treatment:
Dietary Supplement: Placebo

Trial contacts and locations

1

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Central trial contact

Martin Gotteland, PhD

Data sourced from clinicaltrials.gov

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