Impact of Nutritional Intervention With Probiotics and Prebiotics on Obesity. (MicoBeBioticos)

April 9, 2025 updated by: Alba Rodriguez Nogales, Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental

The Microbiome as a Modifiable and Predictive Factor in Obesity Treatment: Impact of Nutritional Intervention With Probiotics and Prebiotics.

Obesity is one of the most severe and prevalent non-communicable diseases worldwide, affecting an estimated one-third of the population in Spain. It is a multifactorial disease that, in extreme cases such as morbid obesity, can become highly disabling and is associated with significant morbidity and mortality. This is because it serves as a risk factor for numerous chronic diseases, including metabolic conditions (type 2 diabetes mellitus), cardiovascular diseases (hypertension, atherosclerosis, etc.), and even cancer.

The exact etiopathogenic mechanisms are not fully understood, but subclinical inflammation is considered to form the basis of the metabolic (diabetes) and cardiovascular (endothelial dysfunction, dyslipidemia, etc.) disturbances that almost invariably accompany obesity. Additionally, alterations in the composition of the gut microbiota, or dysbiosis, are now recognized as playing a key role in the pathogenesis of obesity. This makes the gut microbiota a highly attractive therapeutic target for both the prevention and treatment of obesity, including less severe forms and morbid obesity.

In this context, the use of probiotics or extracts with prebiotic properties represents a particularly interesting strategy against obesity, offering a combination of efficacy and safety for treating these patients. Consequently, the general objective is proposed to evaluate the impact of dietary interventions aimed at modulating dysbiosis through the administration of a probiotic (Lactobacillus fermentum CECT5716), a standardized olive leaf extract with prebiotic properties, or a synbiotic (a combination of the olive leaf extract and L. fermentum CECT5716) on the clinical response of patients with moderate or morbid obesity. This will include determining its relationship with the immuno-metabolic system and the characteristic cardiovascular complications of obesity.

Furthermore, the evaluation of these treatments in experimental models of obesity, including morbid obesity requiring surgery, is also proposed. These models will include trials involving fecal material transfer into germ-free mice. These results will add significant value to the project by advancing our understanding of the underlying mechanisms of the disease. This will aid in the establishment of new diagnostic, prognostic, and therapeutic biomarkers, which are of great interest in reducing the incidence and prevalence of this current obesity epidemic.

The estimated duration for completing the project is 12 months, with its conclusion anticipated by March 2024.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Obesity: The Epidemic of the 21st Century and a Public Health Concern. Obesity is one of the most severe and prevalent non-communicable diseases of the 21st century, representing a global public health problem that affects all age groups. In Spain, it is estimated that over 39% of adults (aged 25-60) are overweight and 20% are obese, with Andalusia being one of the regions with the highest rates, which continue to rise. Obesity is a multifactorial, recurrent, and progressive disease associated with significant physical and psychological complications, as well as considerable morbidity and mortality. It is a key risk factor for numerous chronic conditions, including metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia) and the associated elevated risk of cardiovascular diseases.

Moreover, obesity can increase the risk of other diseases, including digestive, respiratory, and joint disorders, as well as various types of cancer (esophagus, colon, pancreas, prostate, and breast). Although the pathogenic mechanisms underlying obesity are not fully elucidated, it is understood that obesity is linked to a state of chronic low-grade systemic inflammation. Dysregulated adipose tissue functionality in obese individuals leads to elevated free fatty acid levels and increased production of inflammatory cytokines, establishing a vicious cycle that promotes the hypertrophy and hyperplasia of adipocytes, hallmarks of obesity.

The excessive production of these mediators and their release into the bloodstream have a profound impact on other organs and systems, contributing to the metabolic (e.g., diabetes) and cardiovascular (e.g., endothelial dysfunction, atherosclerosis) alterations that almost invariably accompany obesity. Consequently, obesity is associated with reduced quality of life and has a significant negative socioeconomic impact. It is also a determinant of several "intermediate risk factors," leading to increased mortality and reduced life expectancy.

The treatment of obesity involves lifestyle and dietary changes, often supplemented by pharmacological therapy, including appetite suppressants and fat absorption inhibitors. However, these strategies may be insufficient, and for severe obesity (BMI >35) or morbid obesity (BMI >40), surgical intervention is often necessary. Bariatric surgery, despite its effectiveness in reducing metabolic and cardiovascular comorbidities and improving survival and quality of life, involves significant complications due to patient characteristics and high costs. Moreover, over the last 30 years, there has been a marked increase in the prevalence of morbid obesity and, consequently, a greater demand for bariatric surgery.

While surgery reduces comorbidities and enhances patient outcomes, its effects on the gut microbiota remain suboptimal. As such, specific dietary interventions before and/or after surgery are needed to improve microbial gene richness and ensure long-term metabolic health.

The Gut Microbiome as a Modifiable Factor in Obesity. Numerous studies have highlighted the critical role of the gut microbiome in the development and maintenance of obesity and its associated conditions. Research shows that the microbiome composition in lean individuals differs significantly from that in obese individuals, a condition known as dysbiosis. Obese individuals exhibit an increased Firmicutes/Bacteroidetes ratio, reduced microbial diversity, and enhanced energy extraction efficiency from food.

Dysbiosis is also associated with increased intestinal permeability, allowing bacterial components such as lipopolysaccharides (LPS) to enter systemic circulation, which promotes endotoxemia and exacerbates inflammation. This altered microbial composition is linked to increased production of short-chain fatty acids (SCFAs), particularly propionate, which may contribute to lipogenesis and gluconeogenesis.

Severe dysbiosis is observed in morbidly obese patients, characterized by drastic reductions in microbial richness, intensified systemic inflammation, and metabolic disturbances. Although bariatric surgery improves weight, metabolic markers, and microbial diversity, it does not restore microbiota richness to levels observed in lean individuals. Therefore, dietary interventions targeting microbial restoration are critical for post-surgical recovery and long-term health.

Modulation of the Microbiome in Obesity: Probiotics and Prebiotics. The selective modulation of the gut microbiome using probiotics and prebiotics has emerged as a promising therapy for obesity. Probiotics, defined as live microorganisms that confer health benefits when administered in adequate amounts, offer several advantages, including strengthening the intestinal barrier, immunomodulation, and restoring dysbiosis. Commonly used probiotics in obesity management include strains from the Lactobacillus and Bifidobacterium genera.

Studies in both animal models and humans have demonstrated that specific strains can reduce body weight, fat accumulation, lipid profiles, and inflammatory markers. However, the overall efficacy in humans has been modest, necessitating further research to identify optimal strains, dosages, and treatment durations.

Lactobacillus fermentum CECT5716 has shown immunomodulatory properties in experimental models of colitis and hypertension. Preliminary unpublished studies suggest that it can reduce weight gain and systemic inflammation in obesity models, likely by improving dysbiosis and intestinal barrier function.

Prebiotics, non-digestible dietary components that selectively stimulate beneficial gut bacteria, are also effective in obesity management. Phenolic compounds, such as oleuropein from olive leaves, have shown significant prebiotic potential, reducing fat deposition, improving lipid and glucose profiles, and mitigating inflammation and vascular dysfunction in animal studies.

The current project aims to evaluate the effects of dietary supplementation with L. fermentum CECT5716 or a standardized olive leaf extract, alone or in combination, on clinical outcomes in patients with moderate and morbid obesity. Specifically, it will assess their impact on dysbiosis, metabolic and cardiovascular health, and post-surgical recovery in morbidly obese patients. The intervention's effectiveness will be correlated with adherence to a Mediterranean diet. By integrating microbiomic and metabolomic analyses, the study seeks to establish a personalized treatment framework for obesity.

H1: L. fermentum CECT5716 and/or olive leaf extract supplementation reduces inflammation, metabolic disturbances, and cardiovascular complications in obesity.

H2: These interventions restore dysbiotic gut microbiota composition and function.

H3: Supplementation improves post-operative outcomes in morbidly obese patients.

H4: Combining probiotic and prebiotic interventions provides synergistic benefits, maximizing efficacy.

This project offers a comprehensive approach to addressing obesity through microbiome modulation, paving the way for innovative, personalized therapeutic strategies.

Study Type

Interventional

Enrollment (Estimated)

230

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Granada, Spain, 18016
        • Centro de Investigacion Biomedica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Clinical Diagnosis of Obesity and Associated Comorbidities (Prediabetes, Diabetes, Dyslipidemia, Hypertension).

Exclusion Criteria:

  • Antibiotic treatment.
  • Pregnancy.
  • Clinical diagnoses of Inflammatory bowel disease.
  • Clinical diagnosis of Celiac disease
  • Clinical diagnosis of Hematological pathologies.
  • Clinical diagnosis of Autoimmune or immunodeficiency diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo treated with 500 mg/capsule/day of maltodextrin
Dietary supplement: Probiotic
Treatment with capsules with 10^9 CFU/ day of Limosilactobacillus fermentum CECT5716 during 6 months
Dietary supplement: Prebiotic
Treatment with capsules 500 mg/capsule/day of olive leaf extract, containing 35% oleuropein during 6 months
Dietary supplement: Synbiotic
A pill with a combination of prebiotic and probiotic at the same doses during 6 months
Active Comparator: Probiotic
capsules with 10^9 CFU/ day of Limosilactobacillus fermentum CECT5716
Dietary supplement: Prebiotic
Treatment with capsules 500 mg/capsule/day of olive leaf extract, containing 35% oleuropein during 6 months
Dietary supplement: Synbiotic
A pill with a combination of prebiotic and probiotic at the same doses during 6 months
Active Comparator: Prebiotic
500 mg/capsule/day of olive leaf extract, containing 35% oleuropein, an amount comparable to what could be consumed through daily intake of extra virgin olive oil.
Dietary supplement: Probiotic
Treatment with capsules with 10^9 CFU/ day of Limosilactobacillus fermentum CECT5716 during 6 months
Dietary supplement: Synbiotic
A pill with a combination of prebiotic and probiotic at the same doses during 6 months
Active Comparator: Symbiotic
A combination of prebiotic and probiotic at the same doses.
Dietary supplement: Probiotic
Treatment with capsules with 10^9 CFU/ day of Limosilactobacillus fermentum CECT5716 during 6 months
Dietary supplement: Prebiotic
Treatment with capsules 500 mg/capsule/day of olive leaf extract, containing 35% oleuropein during 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the composition of the intestinal microbiome using metagenomic analysis
Time Frame: From enrollment (T0) to the end of treatment (6 months(T6))
Microbial DNA will be isolated from the intestinal contents (feces) of different groups at various time points (T0 and T6). Taxonomic group identification will be performed through metagenomic sequencing using the Nextera XT Library Preparation Kit (Illumina). Sequencing will be conducted on a NovaSeq-6000 platform. To analyze the microbiota taxonomy, the RAST platform will be used to classify reads into different amplicon sequence variants (ASVs). A dynamic threshold will be applied to filter out false or incorrect ASVs, eliminating those contributing less than 0.1% of the total sequence count. The ASVs table will then be normalized per sample using subsampling (or rarefaction) to a minimum read count. QIIME wrapper scripts (v1.9.1) will be employed to classify reads into taxonomic units and to identify taxa with differential abundance between groups.
From enrollment (T0) to the end of treatment (6 months(T6))
Evaluation of the treatment using integrated data analysis
Time Frame: From enrollment (T0) to the end of treatment (6 months(T6))

The data obtained from the different determinations conducted will be automated for integrated analysis. Variables will be normalized, and qualitative variables will be categorized.

Integrated bioinformatics analysis will compare and functionally correlate nutritional data, omics data (microbiomics, metabolomics, and immunological profiles) with clinical phenotypes (obese and morbidly obese patients) and treatments (probiotic, prebiotic, and synbiotic).

This analysis will be based on Bayesian methods, which provide a statistical framework enabling the probabilistic integration of information across multiple analysis steps. All data will be analyzed using R and GraphPad Prism (version 8.4.1). This approach will allow the identification of relationships between microbiota impact and the administered treatments, as well as determine which treatment demonstrated the highest efficacy.
From enrollment (T0) to the end of treatment (6 months(T6))

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of serological biochemical profile
Time Frame: From enrollment to the end of treatment (6 months)
In blood samples collected at different points of the study (baseline and endpoint), the following parameters will be assessed using an autoanalyzer (Beckman Coulter AU5800): serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT), total bilirubin, creatinine, uric acid, and lipid profile, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Serum leptin, IL-6, and TNF-α will be measured using the MILLIPLEX MAG Human Adipokine Magnetic Bead Panel (Millipore). Serum adiponectin, lipopolysaccharide-binding protein (LBP), and insulin will be quantified using ELISA kits. All variables will be quantified in IU/L.
From enrollment to the end of treatment (6 months)
Determination of the treatment impact on the metabolome profile
Time Frame: From enrollment (T0) to the end of treatment (6 months(T6))
Metabolomic studies from serum samples at two different points (initial and final point) will be performed usign HPLC-GS-GC (min and m/z).
From enrollment (T0) to the end of treatment (6 months(T6))

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2024

Primary Completion (Actual)

March 1, 2025

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

November 22, 2024

First Submitted That Met QC Criteria

December 3, 2024

First Posted (Actual)

December 9, 2024

Study Record Updates

Last Update Posted (Actual)

April 11, 2025

Last Update Submitted That Met QC Criteria

April 9, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Fundación Pública Andaluza par

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metabolic Syndrome

Clinical Trials on Probiotic

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe