Effect of a Postbiotic Supplementation in Overweight and Obese Subjects: A Randomized Controlled Trial (PARABIOTICS-2).

Clinical Evaluation of a Postbiotic Supplement in Overweight and Obese Subjects: A Randomized Controlled Trial.

The principal objective of this project is to evaluate the effect of a postbiotic supplement (inactivated microorganism) on body composition and other physiological and metabolic parameters related to excess body weight in overweight or obese adult men and women, as well as to determine changes in the gut microbiota associated with these outcomes.

Specific objectives are focus on evaluate the effect of the intervention on the following parameters:

• Changes in body weight and composition.
• Changes in glucose tolerance.
• Changes in gut microbiota (metagenomics).
• Changes in urinary and serum metabolites.
• Changes in routine biochemical variables related to carbohydrate and lipid metabolism, as well as liver parameters.
• Changes in specific markers involved in obesity pathology, such as insulin, leptin, adiponectin, and cytokines MCP-1, TNF, CRP, and others.
• Adherence to the nutritional recommendations and the gummy containing postbiotic formula.
• Changes in the level of physical activity.

Target sample size is 114 subjects, including a 10% of drop out.

Participants will be allocated in two groups for 12 weeks:

• Experimental group (n=57): nutritional recommendations + postbiotic supplement/gummy.
• Placebo group (n=57): nutritional recommendations + placebo supplement/gummy.

Participants will visit the nutritional intervention unit at weeks 1 and 12. A follow-up phone call will be conducted at week 6.

Volunteers who wish to participate in the study will complete an online questionnaire to verify eligibility based on the main inclusion criteria. Volunteers who meet these criteria will be invited to an information and screening visit to address any questions. Those who agree to participate will sign the informed consent form, be randomly assigned to one of the two study arms, and receive the necessary study materials.

During the intervention, volunteers will attend two clinical investigation visits. The Clinical Investigation Day 1 will be conducted on the first day of the study, and the Clinical Investigation Day 2 visit will occur at the end of the 12-week intervention. At both visits, anthropometric and body composition measurements, blood pressure, and samples of blood, urine, and stool will be collected. Additionally, data on diet, physical activity, sleep, and gastrointestinal symptoms will be recorded.

Inclusion Criteria:

• Male and female participants aged 18 to 70 years.
• Volunteers with overweight or obesity (BMI: ≥ 27-39.9 kg/m²) and a body fat percentage of ≥ 30% for women and ≥ 20% for men.
• Stable body weight (±5%) for at least the three months prior to study initiation.
• Normal physical examination and vital signs, or clinically non-relevant findings for the purposes of the study (i.e., not related to metabolic health).
• Subjects must be able to understand and willing to sign the informed consent form, and comply with all study procedures and requirements.
• Continued pharmacological/hormonal treatment will be permitted provided it does not affect the study parameters and that the dosage has remained stable at least the previous three months to the start of the intervention. Treatment with insulin or any drug with a hypoglycemic effect will be excluded
• Willingness to undergo all study procedures (including the daily consumption of a 1 g gummy during the intervention).
• Time and geographic availability to attend the two on-site clinical evaluation sessions at the scheduled times (including a 3-hour session during visit 2).

Exclusion Criteria:

• Volunteers undergoing pharmacological treatment will be excluded if the treatment has not been stable for at least 3 months prior to study initiation. Excluded treatments include:
• Those that alter gastrointestinal function.
• Chronic use of stomach protectors.
• Any hypoglycemic drugs or insulin.
• Subjects with significant functional or structural abnormalities of the digestive system, such as malformations, angiodysplasias, active peptic ulcers, chronic inflammatory or malabsorption diseases, hiatal hernia, chronic reflux, etc.
• Subjects who have undergone surgical interventions resulting in permanent sequelae in the digestive tract (e.g., gastroduodenostomy) or bariatric surgery.
• Subjects with chronic metabolic diseases or obesity-related conditions, or systemic intestinal, hepatic, or renal diseases, including type 1 or 2 diabetes, severe dyslipidemia, uncontrolled thyroid disorders, cirrhosis, inflammatory bowel disease, untreated anemia, etc. (Non-alcoholic fatty liver disease will not be an exclusion criterion).
• Exceeding the alcohol consumption limit established for each sex (more than 14 units per week for women and 20 units per week for men).
• Pregnant or breastfeeding women, or those planning to become pregnant.
• Use of nutritional supplements (such as weight loss supplements, newly initiated fiber supplements, probiotics, postbiotics, etc.) containing compounds that may affect study outcomes, unless the participant agrees to discontinue them during the 12-week intervention period and a minimum 15-day washout period prior to baseline measurements is ensured.
• Blood donation within 14 days prior to the baseline visit.
• Subjects with any type of cancer or undergoing cancer treatment, or for whom less than 5 years have passed since remission.
• Subjects allergic to any component of the study product or to any other food that could interfere with or hinder study compliance.
• Subjects presenting any type of cognitive and/or psychiatric impairment.
• Subjects anticipated to have poor compliance or who, in the investigator's opinion, may have difficulty adhering to study procedures.
• Subjects currently undergoing treatment for weight loss or body composition modification.
• Subjects who are taking or have taken antibiotics within 60 days prior to the baseline visit.