Probiotic Intervention, Bile Acids and Lipid Metabolism Metabolic Profile in Healthy Overweight Subjects.
Condition: Probiotic Intervention
MeSH terms: Overweight
Study type: Interventional

Summary: 
      Moderate hypercholesterolemia, metabolic alterations derived from overweight or obesity, and
      consequently and their related cardiovascular risks can be reduced through changes in
      lifestyle. A growing body of evidence shows a relationship between hypercholesterolemia and
      dysfunction of the gut microbiota.

      Gut microbiota is considered a keystone in maintaining the health condition of the host
      through multiple mechanisms affecting different metabolic processes, including lipid
      metabolism and cholesterol-related pathways. Bile acids (BA) are cholesterol-derived
      compounds synthesized in the liver and metabolized upon modification by gut bacteria once
      they reach the colon.

      Conversely, BAs shape the composition and function of the intestinal microbiota. This mutual
      interplay between BAs and gut microbiota regulates many physiological processes, including
      the lipid, carbohydrate and energy metabolism of the host.

      Previous studies based on Lactobacillus plantarum have shown 3 strains CECT 7527, 7528, and
      7529 with the ability to adhere to the intestinal mucosa with very low toxicity, what makes
      them susceptible to be used as a probiotic. The lipid-lowering effect of the 3 bacteria
      strains was already evidenced in previous preclinical studies in animal models and clinical
      studies in hypercholesterolemic subjects. Up to now, however, little is known about the
      effects of the 3- combined Lactobacillus plantarum strains on levels and profile of bile
      acids in healthy overweight subjects, otherwise at low cardiovascular risk.

      The aim of this study is to explore on the mechanism of action of a Lactobacillus plantarum
      mixture (CECT 7527, CECT 7528 and CECT 7529) and evaluate the effect of this probiotic
      formulation on BA profile as well as on plasma lipids and other related biomarkers when
      administered in a dose-dependent regime in a cohort of overweight subjects.

      The probiotic product was administrated for 4 weeks with a weekly dose-regime of 2x, 3x, and
      4x, respectively, in the second, third, and fourth week in relation to the first week. The
      effects were evaluated on: (1) level and profile of bile acids in plasma and feces, (2)
      plasma lipid/lipoprotein and fatty acid profile and (3) endocrine hormones, glucose
      metabolism and inflammatory markers in plasma.
    

Detailed description: 
      Sample size (N=20) was calculated according results of previous studies on plasma bile acids.
      The study refers to healthy overweight [body mass index (BMI) 25.0-29.9 kg/m2] adult men
      (N=10) and women (N=10) between the ages of 25 and 60 years.

      The study was approved by the Human Ethical Review Committee of the Hospital Sant Pau in
      Barcelona (register number: 20/029). Informed written consent was obtained from all
      participants before their inclusion in the study. To confirm health status, all subjects
      underwent a complete physical examination conducted by the study physician.

      The study lasted 6 weeks that were structured in:

        -  2 weeks of run-in.

        -  4 weeks of intervention period divided into 4 phases of 7 days. During the intervention
           period, Lactobacillus plantarum capsules were consumed according to the following
           pattern:

             -  Days 0-6: 1 capsule/day

             -  Days 7-13: 2 capsules/day

             -  Days 14-20: 3 capsules/day

             -  Days 21-27: 4 capsules/day

      The volunteers visited the center at the beginning of each phase of the intervention period
      (Days 0, 7, 14 and 21) and at the end of the intervention period (Day 28).

      Dietary habits were collected. Compliance was monitored by weekly telephone contact with
      participants and interviewing them at the end of each intervention period. Blood samples were
      collected early at the morning after twelve-hour fasting at baseline and at the end of each
      intervention phase. Blood samples were used for determining all variables of the study. Stool
      samples were obtained at baseline and after 28 days intervention for the study of bile acids,
      fatty acids and microbiota.
    

Intervention name(s): Probiotic preparation of three Lactobacillus plantarum strains (CECT 7527, CECT 7528, CECT 7529)
Intervention type(s): Dietary Supplement
Intervention description(s): All subjects were submitted to 4 weeks intervention consisting on a dose-dependent regime of Lactobacillus plantarum AB-B (strains CECT 7527, CECT 7528, CECT 7529; AB-LIFE). Before starting the intervention period, all subjects were submitted to a 2-weeks run-in period. During the wash-in and intervention-periods, participants were instructed to maintain their habitual dietary habits and to continue their normal pattern of physical activity throughout the study period.
Treatments during the intervention period were: Week 1: 1 capsule/day taken during breakfast; Week 2: 2 capsules / day at- breakfast; Week 3: 2 capsules at breakfast and 1 at dinner; Week 4: 2capsules at breakfast and 2 capsules at dinner. Each capsule contains 1.2x10^9 cfu (colony forming units) in a 1: 1: 1 ratio of the three strains.
Other intervention name(s): AB-LIFE
Intervention model: Single Group Assignment
Intervention model description: The intervention trial consisted of a single-center, one-arm study with a total duration of 8 weeks, which includes 2-weeks run-in period, 4 week intervention period and 2-weeks post-intervention or wash-out period. The intervention period was divided in 4 periods of 7 days each and the treatment consisted of increasing dose of Lactobacillus plantarum AB-B (CECT 7527, CECT 7528, CECT 7529).
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Microbiota; Bile acids; Lipids; Inflammation; Metabolism