Mediterranean-like Unprocessed (CLEAN-MED) Diet Intervention Study of the Gut Microbiome of Healthy Adults

Study Description:

This study (called the CLEAN-MED Diet Study) seeks to examine associations between the gut microbiome, well-being, and adherence to a Mediterranean-like unprocessed food diet. The premise of this study is based on the well-known health benefits of a healthy Mediterranean diet and the potential role that the gut microbiota may serve as a factor in health and disease. The study will recruit healthy outpatient adults, who agree to adhere to a strict Mediterranean-like diet with unprocessed foods, meticulously log their food intake and perceived quality of life using provided questionnaires/tools, and who agree to collect periodic biological samples for analysis. The study will consist of: (1) a short-term cohort who will complete a crossover study design with their habitual Western diet for 4 weeks and the intervention Mediterranean-like unprocessed food diet for 4 weeks (with CLEAN-MED diet food provided by the NIH metabolic kitchen), and (2) a long-term cohort who will continuously adhere to the Mediterranean-like unprocessed food diet for 12 months, following assessment of their baseline diet (with some CLEAN-MED diet foods provided for up to the first 2 weeks of the long-term study, after which the participants must provide their own food).

Objectives:

Primary Objective:

-The primary objective is to measure changes within the gut microbiome in healthy adults who adhere to a Mediterranean-like unprocessed food diet plan.

Secondary Objectives:

• Identify associations between Mediterranean-like unprocessed food diet adherence and psychosocial variables, such as perceived quality of life.
• Identify associations between changes in the gut microbiome and additional biomarkers.

Tertiary Objective:

-Measure the level of adherence to the diet given a strict request for data submission.

Endpoints:

Primary Endpoint:

-Measure changes in gut microbiota composition and functionality from periodic stool sampling using either 16S rRNA and/or shotgun sequencing.

Secondary Endpoints:

• Identify associations between Mediterranean-like unprocessed food diet adherence with perceived quality of life using surveys/questionnaires.
• Measure biomarkers in various biological specimens (stool, blood, and urine) using the pertinent biochemical assays.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Ability of subject to understand and the willingness to sign a written informed consent document
• Age 18-60, at the time of consent
• Willingness to adhere to the dietary regimen and report any major stressors that occur during the study (i.e. changing jobs, moving, death of a close relative/friend, etc.)
• Willingness to provide blood and stool specimens as specified
• BMI >=18 and <= 35 kg/m^2
• Access to necessary resources for participating in a technology-based intervention: computer, smartphone, internet access, etc.
• Has the ability/transportation methods to attend on-site visits
• For 50 of the 60 participants in short-term cohort and for 40 of the 50 participants in the long-term cohort: Currently following a Western diet with PREDIMED-17 MedDiet score <= 7 for >= 1 months and a CLEAN-MED NOVA score of >= 35% kcal in NOVA 4 category with >= 14 items/week in NOVA 4
• For 10 of the 60 participants in short-term cohort and for 10 of the 50 participants in the long-term cohort: Currently following a Western diet with PREDIMED-17 MedDiet score <= 10 for >= 1 months and a CLEAN-MED NOVA score of >= 20% kcal in NOVA 4 category with >= 7 items/week in NOVA 4
• CLEAN-MED Logging Score of >= 43 after initial trial week to continue in the study for the randomization step
• For long-term cohort only: Have resources and capability to consume freshly-cooked (i.e. not pre-packaged or frozen) meals

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study, at the discretion of the PI:

• Current use of medications or dietary supplements for weight or appetite control, whether prescribed or not, including laxatives (within the last 4 weeks)
• Currently eating a vegan, vegetarian, keto or other restrictive diet plan, or food allergies that would affect eating the study diet, at the discretion of the PI
• Active cardiovascular disease (in past year with myocardial infarction, coronary stent or bypass surgery)
• Diabetes (type 1 and 2) or history of gestational diabetes or on hypoglycemic medications or any other indication
• Kidney disease (eGFR less than 50 mL/min per 1.73 m^2)
• Liver disease (liver transaminase higher than 3 times the normal range for the laboratory)
• Symptomatic gallstones
• History of active cancer in the past 3 years except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision
• Has a diagnosed autoimmune condition (i.e. HIV, lupus, etc.) or other immunosuppressive or immunodeficient state, at the discretion of the PI
• Musculoskeletal disorders precluding regular physical activity
• Consumption of the following drugs: proton pump inhibitors, antidiabetic drugs, cholesterol lowering drugs, SGLT-2 inhibitors, GLP-1 receptor agonist, insulin, Amylin analog, Alpha-glucosidase inhibitor, Dopamine agonist, Bile acid sequestrant, corticosteroids, methotrexate or immunosuppressive cytotoxic agents
• Some types of abdominal surgery, including bariatric surgery, or severe intestinal problems (by discretion of study physician), including:

• Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn s disease (mild-moderate-severe), or indeterminate colitis;
• Irritable bowel syndrome (IBS) (moderate-severe);
• Persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated);
• Chronic constipation
• Consumes more than 3 alcoholic beverages per day
• Currently receiving or has received antibiotics, antifungals, antivirals, or antiparasitics in past 2 months
• Is currently using or has used probiotic supplements within the last 2 months
• Is currently on a weight-loss program or has experienced a weight change (gain or loss) of greater than 15 pounds in the past 3 months
• Has a history of hospitalization for mental health condition and/or has had a change in depression or anxiety prescription medications within the past 10 weeks (by discretion of study physician)
• Is pregnant or breastfeeding or planning pregnancy within the time of the study
• Subjects who are not fluent in English
• Use of smoking or chewing tobacco, e-cigarettes, cigars, or other nicotine-containing products, or cannabis
• Regular use of prescription opiate pain medication
• Weight <100 lbs
• Acute disease, defined as the presence of a moderate or severe illness with or without fever, at the time of enrollment
• Inability to communicate effectively with study personnel
• Lack of commitment with the intervention or non-compliance (at the discretion of the investigator)
• Eating disorders