Probiotic Intervention, Bile Acids and Lipid Metabolism Metabolic Profile in Healthy Overweight Subjects.

NCT05378230 | Completed DMC

• 1 other identifier: IIBSP-PRO-2019-122
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Probiotic Intervention

Keywords

Microbiota; Bile acids; Lipids; Inflammation; Metabolism

Outcome Measures

Primary Outcomes (14)

• Change from Baseline Lipid profile at 7 days

  By standardized biochemical techniques

  At days 0 and 7

• Change from Baseline Lipid profile at 14 days

  By standardized biochemical techniques

  At days 0 and 14

• Change from Baseline Lipid profile at 21 days

  By standardized biochemical techniques

  At days 0 and 21

• Change from Baseline Lipid profile at 28 days

  By standardized biochemical techniques

  At days 0 and 28

• Change from Baseline Serum bile acids at 14 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 14

• Change from Baseline Serum bile acids at 28 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 28

• Change from Faecal bile acids at 28 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 28

• Change from Baseline Serum fatty acids at 14 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 14

• Change from Baseline Serum fatty acids at 28 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 28

• Change from Baseline Faecal fatty acids at 28 days

  By ultra-high performance liquid chromatography - mass spectrometry (UHPLC-MS)

  At days 0 and 28

• Change from Baseline Serum lipoprotein profile at 14 days

  By nuclear magnetic resonance (NMR)

  At days 0 and 14

• Change from Baseline Serum lipoprotein profile at 28 days

  By nuclear magnetic resonance (NMR)

  At days 0 and 28

• Change from Baseline Plasmatic endocrine hormones and metabolic markers at 14 days

  By Enzyme-Linked immunosorbent Assay (ELISAs)

  At days 0 and 14

• Change from Baseline Plasmatic endocrine hormones and metabolic markers at 28 days

  By Enzyme-Linked immunosorbent Assay (ELISAs)

  At days 0 and 28

Secondary Outcomes (6)

• Change from Baseline Plasmatic Inflammatory markers at 14 days

  At days 0 and 14

• Change from Baseline Plasmatic Inflammatory markers at 28 days

  At days 0 and 28

• Change from Baseline LDL susceptibility to oxidation and HDL antioxidant capacity at 14 days

  At days 0 and 14

• Change from Baseline LDL susceptibility to oxidation and HDL antioxidant capacity at 28 days

  At days 0 and 28

• Change from Baseline Serum Vitamin D and thyroid hormones (TSH, T3 & T4) at 14 days

  At days 0 and 14

Study Arms (1)

Probiotic mixture

EXPERIMENTAL

Arm that received Lactobacillus plantarum mixture (CECT 7527, CECT 7528 and CECT 7529)

Dietary Supplement: Probiotic preparation of three Lactobacillus plantarum strains (CECT 7527, CECT 7528, CECT 7529)

Interventions

Probiotic preparation of three Lactobacillus plantarum strains (CECT 7527, CECT 7528, CECT 7529) DIETARY_SUPPLEMENT

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.

Also known as: AB-LIFE

Probiotic mixture

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body Mass index (BMI): Between 25 and 30 Kg / m2

You may not qualify if:

• Eating disorders.
• Subjects with cardiovascular risk factors such as hypercholesterolemia (genetic or secondary), hypertension and diabetes, treated pharmacologically.
• History of ischemic heart disease (and / or previous angina or AMI) or arrhythmia (current or previous).
• Previous strokes and / or peripheral vascular disease.
• Alcohol consumption greater than 60 gr / day.
• Kidney failure (creatinine\> 2 mg / dl).
• Presence of neoplasia.
• Presence of systemic disease.
• Psychiatric illness under treatment with psychotropics.
• Unstabilized thyroid disease.
• Pregnancy or breastfeeding.
• In current treatment with non-steroidal anti-inflammatory drugs, antiplatelet agents, fibrates or statins.

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead
• AB Biotics, SA: collaborator

Study Sites (1)

Institut Recerca-Hospital Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Related Publications (1)

• Padro T, Santisteban V, Huedo P, Puntes M, Aguilo M, Espadaler-Mazo J, Badimon L. Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans. Cardiovasc Res. 2024 May 29;120(7):708-722. doi: 10.1093/cvr/cvae061.

  PMID: 38525555 DERIVED

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 18, 2022
• Study Start: September 1, 2020
• Primary Completion: November 28, 2020
• Study Completion: February 21, 2022
• Last Updated: June 7, 2022

Record last verified: 2022-06

Locations

ES (1)