Diet Education Intervention to Improve Bile Acid-Gut Microbiome for the Prevention of Colorectal Cancer for Patients with an Adenoma

Inclusion Criteria

• Underwent screening or surveillance colonoscopy with removal of at least one adenoma
• Age 18-80 years. * This study will only include adult participants because colorectal carcinogenesis in children is more likely to be related to a cancer predisposition syndrome with distinct biological mechanisms compared with sporadic colorectal cancer in adults. Patients over age 80 will not be enrolled since the dietary mechanism in participants over the age of 80 have not yet been well-characterized
• Habitually consume a Western pattern diet. * Participants must habitually consume a Western dietary pattern, characterized by relatively high intakes of red and processed meats, high-fat dairy products, refined grains, and added sugars, and low intake of fiber-rich plant-based foods. Individuals who habitually follow a Western dietary pattern are more likely to exhibit baseline bile acid profiles associated with increased colorectal cancer risk. Including participants with this dietary background increases the likelihood of observing measurable changes in bile acid production and metabolism in response to the plant-forward dietary intervention, thereby enhancing the study’s ability to assess biological effects of the intervention.
• 18.5 ≤ body mass index (BMI) < 35 kg/m^2. * Participants must have a body mass index (BMI) ≥ 18.5 and < 35 kg/m^2 at the time of enrollment. This BMI range is selected to exclude individuals who are underweight or severely obese, as extreme BMI values may be associated with altered bile acid metabolism, hepatic dysfunction, or comorbidities that could confound study outcomes. Individuals within this BMI range are more likely to have relatively preserved bile acid production and metabolic capacity, improving the interpretability of bile acid responses to dietary intervention
• Weight stable in last 3 months (loss or gain < 4%). * Participants must have maintained a stable body weight (defined as <4% change in body weight) over the past 3 months prior to enrollment. Weight stability over the preceding 3 months is used as a proxy for recent consistency in dietary and energy intake. Individuals with stable weight are more likely to have steady-state metabolic conditions, including normal bile acid production and metabolism. This criterion helps ensure that any changes in bile acid profiles observed during the intervention can be more confidently attributed to the dietary modification rather than to recent shifts in caloric intake, weight loss, or metabolic adaptation
• The effects of dietary modulation on developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
• Subjects must be able and willing to follow study procedures and instructions
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Strict dietary patterns (e.g., vegan, carnivore, kosher, low-carb etc)
• Known allergies or hypersensitivity to nuts, soy, fish, or other foods included in the study dietary intervention. * Participants with such allergies will be excluded to ensure safety and avoid adverse reactions during the intervention period. Because the dietary intervention emphasizes increased consumption of nuts, soy-based foods, and fish, inclusion of individuals with such allergies could pose significant health risks and compromise adherence
• Diagnosis of inflammatory bowel disease, liver disease with evidence of clinical decompensation or chronic kidney disease (grade 3-4), bleeding diathesis
• Any prior diagnosis of invasive (i.e. excluding intramucosal cancer) gastrointestinal cancer (including esophageal, small intestine, colon, pancreatic), or any diagnosis of other cancers (with the exception of nonmelanoma skin) in which there has been any active treatment within the last three years
• Known diagnosis of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch Syndrome)
• Any adenoma that was not completely removed during previous colonoscopy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Regular use of aspirin. * Participants who report regular use of aspirin (defined as ≥ 2 times per week over the past 3 months) will be excluded. Regular use of aspirin has been associated with a reduced risk of colorectal neoplasia through its anti-inflammatory and chemo preventive effects. Including individuals who regularly use aspirin may confound the study’s ability to isolate the impact of the dietary intervention on bile acid metabolism and colorectal cancer risk markers. Therefore, to preserve internal validity and reduce potential bias, regular aspirin users will be excluded
• Use of antibiotics or probiotics. * Participants who have used systemic antibiotics or probiotic supplements within the past 90 days will be excluded. Recent use of antibiotics or probiotics can significantly alter the composition and function of the gut microbiome. Because the study aims to evaluate changes in bile acid metabolism that are partly mediated by gut microbial activity, prior microbiome-altering exposures could confound the interpretation of intervention effects. A 90-day washout period helps ensure a more stable baseline microbial environment, allowing for more accurate assessment of diet-induced changes
• Inability or unwillingness to abstain from limited consumption of animal-based food or to provide blood or stool samples during the study
• Participants who are receiving investigational agents
• Pregnant or breastfeeding
• Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection. * Participants with these infections are ineligible because they are at increased risk of significant complications in the perioperative period. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated