Bariatric Surgery Versus Diet Alone in the Bile Acid Pathway and Weight Loss

Participants will be placed into two groups. The Roux-En-Y Gastric Bypass (RYGB) group will
consist of participants who will have elected to have RYGB at the Mayo Clinic Bariatric
Center of Excellence. The Diet group will have a low-calorie diet prescribed by a registered
dietitian. Both groups will collect stool from every bowel movement 2 days before presenting
for baseline testing. Both group participants will present for baseline testing after an
overnight fast and before intervention (RYGB or low calorie diet). Participants will consume
a standard breakfast provided by study staff and blood samples will be collected at -15, 0,
15, 30,45,60,90,120,150,180,210,240,300,360 minutes. Appetite and satiation ratings will be
recorded via questionnaires during that day every 15 minutes for the first 90 minutes, then
every 30 minutes. Participants will repeat this regimen again after losing 7% of their body
weight after having RYGB or low calorie diet.

Inclusion Criteria:

- Women of childbearing potential will have negative pregnancy tests within 48 hours of
enrolment.

- BMI: ≥ 40

- Individuals who have elected to have RYGB at the Mayo Clinic Bariatric Center of
Excellence, and individuals with a BMI ≥40 who are otherwise healthy with controlled
cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, or
endocrine disorders. The RYGB participants will be invited to participate when their
surgery is scheduled at the Mayo Clinic Bariatric Center of Excellence.

- The non-RYGB participants (BMI ≥40) will be otherwise healthy individuals with no
unstable psychiatric disease and no unstable cardiac, pulmonary, gastrointestinal,
hepatic, renal, hematological, neurological, or endocrine disorders.

Exclusion Criteria:

- History of abdominal surgery including cholecystectomy and other than appendectomy,
Caesarian section or tubal ligation.

- Positive history of chronic gastrointestinal diseases, or systemic disease that could
affect gastrointestinal motility, or use of medications that may alter
gastrointestinal motility, appetite or absorption, e.g., orlistat, phentermine.

- Significant untreated psychiatric dysfunction based upon screening with the Hospital
Anxiety and Depression Inventory (HAD), a self-administered alcoholism screening test
(AUDIT-C) and the Questionnaire on Eating and Weight Patterns (binge eating disorders
and bulimia). If such a dysfunction is identified by a depression or anxiety score >11
or difficulties with substance or eating disorders, the participant will be excluded
and given a referral letter to his/her primary care doctor for further appraisal and
follow-up. The AUDIT-C is a 3-item alcohol screening questionnaire that reliably
identifies participants who are hazardous alcohol drinkers or have active alcohol use
disorders. In men, a score of 4 or more is above the recommended limits will be
reviewed by study personnel. In women, a score of 3 or more is above the recommended
limits will be reviewed by study personnel. However when the points are above
recommended limits, the provider will review the patient's alcohol intake over the
past few months to confirm accuracy and determine study eligibility.

- Any acute or chronic condition or other disease that, in the opinion of the
Investigator, would limit the subject's ability to complete and/or participate in this
clinical study.Participant activities:

- If recruited for the investigation participants will be asked to refrain from donating
blood; refrain from participating in other research studies; avoid taking any
additional over the counter or prescription medications or herbal supplements that
have not been reviewed and approved by the physician or the study coordinator until
the study has been completed