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

• 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 informedconsent document

• Age 18-60, at the time of consent

• Willingness to adhere to the dietary regimen and report any major stressors thatoccur during the study (i.e. changing jobs, moving, death of a closerelative/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 participantsin the long-term cohort: Currently following a Western diet with PREDIMED-17 MedDietscore <= 7 for >= 1 months and a CLEAN-MED NOVA score of >= 35% kcal in NOVA 4category with >= 14 items/week in NOVA 4

• For 10 of the 60 participants in short-term cohort and for 10 of the 50 participantsin the long-term cohort: Currently following a Western diet with PREDIMED-17 MedDietscore <= 10 for >= 1 months and a CLEAN-MED NOVA score of >= 20% kcal in NOVA 4category with >= 7 items/week in NOVA 4

• CLEAN-MED Logging Score of >= 43 after initial trial week to continue in the studyfor 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 foodallergies that would affect eating the study diet, at the discretion of the PI

• Active cardiovascular disease (in past year with myocardial infarction, coronarystent or bypass surgery)

• Diabetes (type 1 and 2) or history of gestational diabetes or on hypoglycemicmedications 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 thelaboratory)

• Symptomatic gallstones

• History of active cancer in the past 3 years except for squamous or basal cellcarcinomas of the skin that have been medically managed by local excision

• Has a diagnosed autoimmune condition (i.e. HIV, lupus, etc.) or otherimmunosuppressive 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 intestinalproblems (by discretion of study physician), including:

• Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn s disease (mild-moderate-severe), orindeterminate colitis;

• Irritable bowel syndrome (IBS) (moderate-severe);

• Persistent, infectious gastroenteritis, colitis or gastritis, persistent orchronic 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, orantiparasitics 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 orloss) of greater than 15 pounds in the past 3 months

• Has a history of hospitalization for mental health condition and/or has had a changein depression or anxiety prescription medications within the past 10 weeks (bydiscretion 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 othernicotine-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 orwithout 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 theinvestigator)

• Eating disorders