Impact of Nutritional Intervention With Probiotics and Prebiotics on Obesity.

NCT06722443 | Enrolling By Invitation DMC

• 1 other identifier: Fundación Pública Andaluza par
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity and Overweight; Obesity, Morbid; Metabolic Syndrome

Keywords

microbiome; obesity; metabolic syndrome; probiotics; prebiotics; symbiotics

Outcome Measures

Primary Outcomes (2)

• Evaluation of the composition of the intestinal microbiome using metagenomic analysis

  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

  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 Outcomes (2)

• Evaluation of serological biochemical profile

  From enrollment to the end of treatment (6 months)

• Determination of the treatment impact on the metabolome profile

  From enrollment (T0) to the end of treatment (6 months(T6))

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo treated with 500 mg/capsule/day of maltodextrin

Dietary Supplement: Probiotic; Dietary Supplement: Prebiotic; Dietary Supplement: Synbiotic

Probiotic

ACTIVE COMPARATOR

capsules with 10\^9 CFU/ day of Limosilactobacillus fermentum CECT5716

Dietary Supplement: Prebiotic; Dietary Supplement: Synbiotic

Prebiotic

ACTIVE COMPARATOR

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; Dietary Supplement: Synbiotic

Symbiotic

ACTIVE COMPARATOR

A combination of prebiotic and probiotic at the same doses.

Dietary Supplement: Probiotic; Dietary Supplement: Prebiotic

Interventions

Probiotic DIETARY_SUPPLEMENT

Treatment with capsules with 10\^9 CFU/ day of Limosilactobacillus fermentum CECT5716 during 6 months

Placebo; Prebiotic; Symbiotic

Prebiotic DIETARY_SUPPLEMENT

Treatment with capsules 500 mg/capsule/day of olive leaf extract, containing 35% oleuropein during 6 months

Placebo; Probiotic; Symbiotic

Synbiotic DIETARY_SUPPLEMENT

A pill with a combination of prebiotic and probiotic at the same doses during 6 months

Placebo; Prebiotic; Probiotic

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental: lead

Study Sites (1)

Centro de Investigacion Biomedica

Granada, Spain, 18016, Spain

Location

Related Publications (4)

• Rodriguez-Sojo MJ, Ruiz-Malagon AJ, Hidalgo-Garcia L, Molina-Tijeras JA, Diez-Echave P, Lopez-Escanez L, Rosati L, Gonzalez-Lozano E, Cenis-Cifuentes L, Garcia-Garcia J, Garcia F, Robles-Vera I, Romero M, Duarte J, Cenis JL, Lozano-Perez AA, Galvez J, Rodriguez-Cabezas ME, Rodriguez-Nogales A. The Prebiotic Effects of an Extract with Antioxidant Properties from Morus alba L. Contribute to Ameliorate High-Fat Diet-Induced Obesity in Mice. Antioxidants (Basel). 2023 Apr 21;12(4):978. doi: 10.3390/antiox12040978.

  PMID: 37107352 BACKGROUND

• Diez-Echave P, Vezza T, Algieri F, Ruiz-Malagon AJ, Hidalgo-Garcia L, Garcia F, Moron R, Sanchez M, Toral M, Romero M, Duarte J, Garrido-Mesa J, Rodriguez-Cabezas ME, Rodriguez-Nogales A, Galvez J. The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome. Biomed Pharmacother. 2022 Sep;153:113445. doi: 10.1016/j.biopha.2022.113445. Epub 2022 Jul 22.

  PMID: 36076560 BACKGROUND

• Molina-Tijeras JA, Diez-Echave P, Vezza T, Hidalgo-Garcia L, Ruiz-Malagon AJ, Rodriguez-Sojo MJ, Romero M, Robles-Vera I, Garcia F, Plaza-Diaz J, Olivares M, Duarte J, Rodriguez-Cabezas ME, Rodriguez-Nogales A, Galvez J. Lactobacillus fermentum CECT5716 ameliorates high fat diet-induced obesity in mice through modulation of gut microbiota dysbiosis. Pharmacol Res. 2021 May;167:105471. doi: 10.1016/j.phrs.2021.105471. Epub 2021 Jan 30.

  PMID: 33529749 BACKGROUND

• Vezza T, Rodriguez-Nogales A, Algieri F, Garrido-Mesa J, Romero M, Sanchez M, Toral M, Martin-Garcia B, Gomez-Caravaca AM, Arraez-Roman D, Segura-Carretero A, Micol V, Garcia F, Utrilla MP, Duarte J, Rodriguez-Cabezas ME, Galvez J. The metabolic and vascular protective effects of olive (Olea europaea L.) leaf extract in diet-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties. Pharmacol Res. 2019 Dec;150:104487. doi: 10.1016/j.phrs.2019.104487. Epub 2019 Oct 11.

  PMID: 31610229 BACKGROUND

MeSH Terms

Conditions

Obesity; Overweight; Obesity, Morbid; Metabolic Syndrome

Interventions

Probiotics; Prebiotics; Synbiotics

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: December 9, 2024
• Study Start: February 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: May 1, 2025
• Last Updated: April 11, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)