Clinical trial NCT01235026: Synbiotics and Low Grade Inflammation in Obese Subjects
Official title: Impact of the Administration of a Synbiotic on Low Grade Inflammation in Obese Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Diabetes Mellitus Type-2
Insulin Resistance
Metabolic Syndrome
Keywords: Obesity
Type-2 Diabetes
Metabolic syndrome
Low grade inflammation
Metabolic endotoxinemia
Insulin resistance
Lipopolysaccharide
LPS-binding protein
sCD14
Synbiotic
Oligofructose
Bifidobacterium animalis subsp. lactis Bb12
probiotic
Prebiotic
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2010-11-05
Enrollment: 44
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasmatic Interleukin-6 (IL-6)
timeFrame: 6 weeks
Secondary outcomes:
measure: Plasmatic LPS-binding protein
timeFrame: 6 weeks
measure: Plasmatic sCD14
timeFrame: 6 weeks
measure: glucose tolerance curve
timeFrame: 6 weeks
measure: Lipid profile
timeFrame: 6 weeks
measure: plasmatic ultrasensitive C-Reactive Protein
timeFrame: 6 weeks
measure: Plasmatic IL-6
timeFrame: 10 weeks
measure: Plasmatic LBP
timeFrame: 10 weeks
measure: Plasmatic sCD14
timeFrame: 10 weeks
measure: Glucose tolerance curve
timeFrame: 10 weeks
measure: Lipid profile
timeFrame: 10 weeks
measure: Plasmatic usCRP
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Institute of Nutrition and Food Technology (INTA), University of Chile
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.