Dietary Intervention to Reduce Metabolic Endotoxemia

Study Overview
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Brief Summary
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The goal of this randomized clinical trial is to compare an antiinflammatory and environmentally friendly dietary strategy (AIA-D) designed based on the planetary health diet recommendations translated to the regional context and including nutrients related to antiinflammatory responses with an active control diet based on general healthy diet recommendations (CONV-D) in adults from 18 to 50 years of age with obesity (body mass index ≥30 kg/m2). The main questions it aims to answer are: If the intervention with AIA-D will cause a significant decrease at the end of the intervention (six weeks) in lipopolysaccharide-binding protein (LBP) compared to CONV-D. If intervention with AIA-D will cause a significant increase at the end of the intervention (six weeks) in the relative abundance of two specific bacteria genera (AM and FP) when compared to CONV-D. Participants will: Sign the informed consent. Provide two peripheral blood samples (taken by our trained professionals). Provide two samples of feces. Allow anthropometric (body weight, height, hip and waist circumferences) blood pressure measurements on two occasions. Respond to 24 h dietary recall on two occasions. Attend the 1-hour group sessions requested (three for AIA-D and one for CONV-D). Follow the dietary recommendations provided. Be willing to participate in social media groups to receive information and follow up during the six weeks of the intervention. Researchers will compare an antiinflammatory and environmentally friendly strategy (AIA-D) with an active control diet (CONV-D) based on general healthy diet recommendations to see if AIA-D decreases metabolic endotoxemia measured through LBP serum levels and increase the relative abundance of AM and FP, compared to CONV-D.

Detailed Description
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This randomized clinical trial proposes to evaluate an environmentally friendly dietary strategy (AIA-D) designed based on the planetary health diet recommendations translated to the regional context and including nutrients related to anti-inflammatory responses that can decrease metabolic endotoxemia and promote FP and AM growth associated with anti-inflammatory effects and good intestinal health compared to an active control diet (CONV-D) general healthy diet recommendations. Primary hypothesis: The intervention with a low-inflammatory and environmentally friendly dietary strategy aimed at adults diagnosed with obesity (body mass index ≥30 kg/m2) will cause a significant decrease at the end of the intervention (six weeks) in the levels of lipopolysaccharide-binding protein (metabolic endotoxemia), and significantly increase the relative abundance of AM and FP, when compared to general healthy diet recommendations. Secondary hypotheses: The intervention with a low-inflammatory and environmentally friendly dietary strategy aimed at adults diagnosed with obesity (body mass index ≥30 kg/m2) will cause a significant increase at the end of the intervention (six weeks) in the relative abundance of Prevotella, when compared to general healthy diet recommendations. The intervention with a low-inflammatory and environmentally friendly dietary strategy aimed at adults diagnosed with obesity (body mass index ≥30 kg/m2) will cause a significant decrease at the end of the intervention (six weeks) of body weight, percentage of body fat, body mass index, circumferences of waist and hip when compared to general healthy diet recommendations. The intervention with a low-inflammatory and environmentally friendly dietary strategy aimed at adults diagnosed with obesity (body mass index ≥30 kg/m2) will improve blood pressure more than the general healthy diet recommendations.

Official Title
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Randomized Controlled Clinical Trial on the Anti-inflammatory Effect of a Sustainable Dietary Strategy in Adults With Obesity

Conditions
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Endotoxemia, Intestinal Microbiota, Dietary Habits, Clinical Trial, Obesity

Intervention / Treatment
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* Behavioral: AIA-D
* Behavioral: CONV-D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obesity according to body mass index: ≥ 30 kg/m2 Willingness to participate and sign the consent form. Willingness to follow the dietary recommendations of the protocol. Have access to the internet and an electronic device. Exclusion Criteria: Clinically diagnosed with hyperglycemia, hypertension, cardiovascular disease, renal disease, hepatic disease, immunosuppression, or another metabolic disease. Being under a dietary restriction regimen or pharmacological treatment to lose weight. Consuming dietary supplements for at least six months (vitamins, fatty acids, probiotics, prebiotics). Being under treatment with antibiotics or anti-inflammatory drugs in the last three months. Having bariatric surgery. Being pregnant or lactating. Present gastrointestinal disease Present Coronavirus disease (COVID-19) symptoms Develop diseases that affect body weight Becoming pregnant Withdrawal of informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An interventional randomized controlled clinical trial of parallel design with active control.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-inflammatory and environmentally friendly dietary strategy (AIA-D)<br>The environmentally friendly dietary strategy (AIA-D) designed based on the planetary health diet recommendations translated to the regional context and includes nutrients related to anti-inflammatory responses | Behavioral: AIA-D<br>* The total energy contribution (1800 kcal/d) is 20% from protein, 25% from lipids, and 55% from carbohydrates. The recommendations include increasing protein intake primarily from plant sources, limiting the intake of red and processed meat, reducing refined sugar, and moderating dairy consumption. It also includes a list of locally produced and seasonal fruits and vegetables and a list of selected ingredients with anti-inflammatory properties to elaborate their foods. Participants will attend 3 motivational sessions of 1 h every two weeks. Besides nutrition and health, the motivational talks focused on the environmental impact of sustainability. Session 1: Planetary healthy diet. The inflammatory potential of diet. Explanation of the program. Session 2. Effect of ultra-processed food on health. Session 3. Healthy diets. Follow-up information, recipes, and pictures of dishes that meet the given recommendations will be sent once a week through closed social media groups.<br>|
| Active Comparator: General healthy diet recommendations (CONV-D).<br>The active comparator CONV-D is based on the general healthy diet recommendations | Behavioral: CONV-D<br>* CONV-D is based on general healthy diet recommendations. The total energy contribution (1800 kcal/d) was 20% from protein, 25% from lipids, and 55% from carbohydrates. Among the recommended food groups are fruits (5 times a day), vegetables (5 times a day), cereals (3 times a day), legumes (3 times a day), dairy products (2 times a day), food of animal origin (3 times per day). Participants in the CONV-D group will attend one motivational and nutritional orientation session on day 1 of the intervention. Session 1. Food and nutrition. Obesity and diet. General healthy diet recommendations. Delivery of material (table of food equivalents). Follow-up information will be sent once a week through closed social media groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lipopolysaccharide-binding protein (LBP). | Peripheral blood samples will be taken before and after the intervention, centrifuged for serum extraction, and stored at -80°C until analysis. ELISA kits were used to quantify LBP. | Baseline to six weeks | 
| Change in relative abundance of FP | According to the manufacturer's instructions, total DNA will be extracted from fecal samples and quantified by a spectrophotometer, where the ratio of 1.8-2.0 (260/280) is acceptable. DNA samples will be stored at -80°C until analysis. FP will be amplified from DNA extracted from fecal samples by quantitative polymerase chain reaction (qPCR). A specific set of primers will be used. The relative expression of the gen (relative abundance) will be calculated. The 16S ribosomal RNA (16S) (V4) normalizing gen will be used for analysis. | Baseline to six weeks | 
| Change in relative abundance of AM | According to the manufacturer's instructions, total DNA will be extracted from fecal samples and quantified by a spectrophotometer, where the ratio of 1.8-2.0 (260/280) is acceptable. DNA samples will be stored at -80°C until analysis. AM will be amplified from DNA extracted from fecal samples by quantitative polymerase chain reaction (qPCR). A specific set of primers will be used. The relative expression of the gen (relative abundance) will be calculated. The 16S ribosomal RNA (16S) (V4) normalizing gen will be used for analysis. | Baseline to six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in abundance of Prevotella | According to the manufacturer's instructions, total DNA will be extracted from fecal samples and quantified by a spectrophotometer, where the ratio of 1.8-2.0 (260/280) is acceptable. DNA samples will be stored at -80°C until analysis. Prevotella will be amplified from DNA extracted from fecal samples by quantitative polymerase chain reaction (qPCR). A specific set of primers will be used. The relative expression of the gen (relative abundance) will be calculated. The 16S ribosomal RNA (16S) (V4) normalizing gen will be used for analysis. | Baseline to six weeks | 
| Change in body weight | Body weight will be measured with minimal clothing using a digital electronic scale (capacity of 0 to 150 ± 0.05 kg). | Baseline to six weeks | 
| Change in body mass index | The body mass index will be calculated by dividing the weight (kg) by the square of height (m). Height will be measured using a stadiometer (rank 0.70-2.05 m) while barefoot participants were standing with their heads in the Frankfurt plane | Baseline to six weeks | 
| Change in hip circumference | The hip circumference will be measured using a flexible anthropometric tape (200 cm) at the widest circumference of the gluteus. | Baseline to six weeks | 
| Change in waist circumference | The waist circumference will be measured using a flexible anthropometric tape (200 cm) at the level of the umbilicus | Baseline to six weeks | 
| Change in waist-to-hip ratio | The waist-to-hip ratio will be calculated by dividing waist circumference (cm) by hip circumference (cm). | Baseline to six weeks | 
| Change in percentage of body fat | An electrical bioimpedance analysis device will measure body fat. | Baseline to six weeks | 
| Change in the dietary inflammatory index. | The DII and energy-adjusted-DII (E-DII) will be calculated from the dietary data collected using 24-h dietary recall for each participant. E-DII scores were calculated using the density approach wherein all nutrients were converted to 1000 kcal consumption. | Baseline to six weeks | 
| Change in blood pressure | Systolic and diastolic blood pressure will be measured by a digital device. | Baseline to six weeks | 
| Retention | Percentage of participants that finished the intervention | Baseline to six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary inflammatory index, Metabolic endotoxemia, Lipopolysaccharide binding protein, Planetary health diet