Therapeutic Potential of a Synbiotic to Improve Mental Health in Subjects With Obesity.

NCT06901739 | Recruiting

• 1 other identifier: PI24/01010
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Obese individuals are a particularly vulnerable population for mental health problems, especially depression and anxiety. The aim of this study is to evaluate whether the intake of a synbiotic, composed of prebiotics and beneficial intestinal bacterial strains, is capable of producing changes in the gut microbiota and its functionality, improving metabolic and inflammatory parameters, intestinal function and appetite control in patients with obesity and psychological disorders. In addition, the production of neurotransmitters at the level of the gut-brain axis will be studied, as well as mood and quality of life. For this purpose, a prospective, randomized, doubleblind, placebo-controlled intervention study will be carried out in patients with obesity (BMI=30-40 kg/m2) and symptoms of anxiety and/or depression, or patients with obesity but without these psychological disorders (n=120). The groups will be randomly divided into two groups (n=60) according to the intake of a synbiotic (1 capsule/day composed of bifidobacterium, Lactobacillus and tannin-based phytocomplexes) or its corresponding placebo for 12 weeks. Individualized psychological and nutritional follow-up will be carried out, demographic, lifestyle and mental health variables will be collected, and biological samples will be collected before and after the intervention. In addition, all patients will undergo an assessment of body composition and nutritional status, together with cardiovascular risk factors and comorbidities (hypertension, dyslipidemia, DM2, insulin resistance). Inflammatory parameters (IL6, TNF , IL1b, adiponectin, PAI-1, IL10, resistin, adipsin), antioxidant capacity, intestinal function (zonulin, LPS, occludin, LBP, FABP2/I-FABP, -glucan, Reg3A), satiety, appetite control (Leptin, GLP1, GIP, Ghrelin, PP) and neurotransmitter production (cortisol, dopamine, serotonin, oxytocin) in plasma/serum, urine or saliva using ELISA Kits and Luminex XMAP technology will be analyzed. In addiition, the investigators will perform analysis of genetic markers of inflammatory and metabolic pathways (Nanostring technology), metabolomic profiling (NMR spectroscopy and PLS-DA) in plasma, and both content and diversity of the intestinal microbiota (16S rRNA amplicons, and direct metagenomic sequencing, with Illumina MiSeq technology) in faeces will be evaluated. Finally, the investigators will study in vitro the mechanism of action of colonic digest on complex cellular models that simulate the gut-brain axis (organ-on-chip model, OoC).

Conditions

Obese Patients (BMI ≥ 30 kg/m²); Anxiety; Depressive Disorder

Keywords

Microbiota; Inflammation; Symbiotic; Tannins; Mental disorders; Obesity

Outcome Measures

Primary Outcomes (4)

• Analyze the changes in the diversity of the intestinal microbiota after the symbiotic intake.

  To assess the alpha-diversity of the intestinal microbiota after the symbiotic intake, defined as the average diversity of species in an ecosystem, the Shannon index will be used. The results are interpreted as follows: values less than 2 are considered low in diversity and values greater than 3 are high in species diversity.

  3 years

• Evaluate the differences in the diversity of the intestinal microbiota depending on whether participants have received the synbiotic or the placebo supplement.

  To assess the alpha-diversity of the intestinal microbiota, defined as the average diversity of species in an ecosystem, the Shannon index will be used. A significant difference between both groups (synbiotic and placebo) will be considered when notable differences are observed in the mean values between groups measured through p-value (\<0.05) with a 95% confidence interval.

  3 years

• Identify and assess the differences in metabolic pathways of gut microbiota after the synbiotic intake.

  Genetic markers of inflammation and metabolic pathways will be analyzed from the faeces samples, in order to identify different clusters of these pathways and determine the potential functions of gut microbiota. For that purpose, transcriptome will be quantified with nanostring techology. The relative quantity of gene expression (fold change) of each gene will be calculated with the comparative 2-ΔΔCT method, and significant differences will be considered when notable differences are observed in the mean values between groups measured through p-value (\<0.05) with a 95% confidence interval.

  3 years

• Assess if there is a significant improvement in psychological parameters of anxiety and depression after the synbiotic intake.

  Psychological parameters will include anxiety and depression symptoms. Anxiety and depression will be quantified using a validated scale called Depression Anxiety and Stress Scale 21 (DASS-21), which focuse on psychological symptoms and to diagnose both anxiety and depression disorders. In this scale, in depression questions, a score of 0-9 indicates normality, 10-13 mild depression, 14-20 moderate depression, 21-27 severe depression, and \>27 extreme severe depression; in anxiety scale, a score of 0-7 reflects normality, 8-9 mild anxiety, 10-14 moderate, 15-19 severe, and \>19 extreme severe anxiety; in stress scale, a score of 0-14 indicates normality, 15-18 mild stress, 19-25 moderate stress, 26-33 severe stress, and \>33 extreme severe stress.

  3 years

Secondary Outcomes (26)

• Evaluate significant changes in body fat mass percentage after the synbiotic intake.

  3 years

• Assess significant changes in high-sensitivity C-reactive protein (hs-CRP) as an inflammatory parameter after the synbiotic intake

  3 years

• Evaluate significant changes in C3 protein as an inflammatory parameter after the synbiotic intake.

  3 years

• Assess significant changes in plasmatic homocysteine as an inflammatory parameter after the synbiotic intake.

  3 years

• Evaluate significant changes in interleukin 1-beta (IL-1B) levels as a pro-inflammatory molecule after the synbiotic intake

  3 years

Study Arms (4)

Synbiotic supplement in subjects with obesity and mental disorders

EXPERIMENTAL

Subjects with both obesity and mental disorders (only including anxiety or depression diagnosed disorders) will recieve the synbiotic supplement and nutritional intervention by a registered dietitian for 12 weeks.

Dietary Supplement: Synbiotic

Synbiotic supplement in subjects with obesity and without mental disorders

ACTIVE COMPARATOR

Subjects with obesity yet without diagnosed mental disorders will recieve the synbiotic supplement and nutritional intervention by a registered dietitian for 12 weeks.

Dietary Supplement: Synbiotic

Placebo in subjects with obesity and mental disorders

PLACEBO COMPARATOR

Subjects with both obesity and mental disorders will recieve nutritional intervention by a registered dietitian and a supplement containing a powder with an identical color compared to the synbiotic supplement.

Dietary Supplement: Placebo

Placebo in subjects with obesity and without mental disorders

PLACEBO COMPARATOR

Subjects with both obesity but no diagnosed mental disorders will recieve nutritional intervention by a registered dietitian and a supplement containing a powder with an identical color compared to the synbiotic supplement.

Dietary Supplement: Placebo

Interventions

Synbiotic DIETARY_SUPPLEMENT

The synbiotic supplement contains both tannins (350mg) and probiotic strains (Lactobacillus acidophilus, Lactobacillus casei, y Bifidobacterium lactis 2×10 9 UFC/g each) that have already demonstrated a positive health effect in obesity. Besides, participants will follow a dietary intervention to improve their dietary habits and reduce weight by a registered dietitian.

Also known as: tannins, probiotic

Synbiotic supplement in subjects with obesity and mental disorders; Synbiotic supplement in subjects with obesity and without mental disorders

Placebo DIETARY_SUPPLEMENT

Subjects will recieve a placebo supplement, contained in an identical capsule form as the synbiotic, along with the same dietary intervention to improve their dietary habits and reduce weight by a registered dietitian.

Placebo in subjects with obesity and mental disorders; Placebo in subjects with obesity and without mental disorders

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with BMI 30-40kg/m2, with at least 5 years of diagnosed obesity evolution.
• Patients have had stable body weight (\<5% of body weight changes) during the 3 months prior to the study.
• Participants between 18 and 65 years of age.

You may not qualify if:

• All patients with acute or chronic inflammatory diseases, neoplasic disease, secondary causes of obesity (uncontrolled hypothyroidism, Cushing's syndrome), or established liver and kidney failure (according to transaminase levels ±2 SD of the mean and estimated glomerular filtration rate using the CKD-EPI formula \>60), previous bariatric surgery, and women during pregancy or lactation, will be excluded.

Sponsors & Collaborators

• Celia Bañuls: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

FISABIO

Valencia, Valencia, 46020, Spain

RECRUITING

Related Publications (36)

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MeSH Terms

Conditions

Anxiety Disorders; Depressive Disorder; Inflammation; Mental Disorders; Obesity

Interventions

Synbiotics; Tannins; Probiotics

Condition Hierarchy (Ancestors)

Mood Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prebiotics; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Polyphenols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Biopolymers; Polymers; Macromolecular Substances

Central Study Contacts

Celia Bañuls Morant, PhD

CONTACT

963188882; celia.banuls@fisabio.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 23, 2025
• First Posted: March 30, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)