Colorectal Cancer, Diet Habit
Conditions
Keywords
Colorectal cancer, Microbiome, Urolithin, Walnuts, Diet habit, Inflammatory markers, Colon inflammation
Brief summary
The purpose of this research study is to examine whether adding walnuts to your diet can have a beneficial effect on the gut bacteria population, inflammatory markers in the blood, and the tissue that lines the inside of the colon.
Detailed description
This is a 30-day dietary intervention study where participants will be asked to consume 2 ounces of walnuts daily for 21 days, and at the end of the study period they will come in for a routine colonoscopy. After being informed about the study and potential risks, participants giving written informed consent will first start a 7-day wash-out period where they will be asked to avoid foods high in ellagitannins for the duration of the study. In addition, participants will be asked to complete food and activity questionnaires, a walnut consumption log, and two sets of 3-day dietary records during their participation in the study. Participants will also be asked to provide three urine samples, two blood samples, and two stool samples at multiple time points, and 8-10 colon tissue specimens (biopsies) will be collected during their colonoscopy procedure for the purposes of this study.
Interventions
OTHERWalnuts
Participants consume 2 ounces of walnuts daily for 21 days
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Weill Medical College of Cornell University
University of Connecticut
California Walnut Commission
Spanish National Research Council
University of Florida
UConn Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
39 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men and women between the ages of 39-75 years old who meet the criteria of one of the following groups and are eligible to undergo a routine screening or surveillance colonoscopy for colorectal cancer (CRC): 1. Individuals who have a family history of colon polyps or CRC in a first-degree relative diagnosed with CRC under the age of 65 years, or 2. Individuals who are referred for colonoscopy following a positive fecal immunochemical test (FIT) or a positive Cologuard screening test and have not had a high-quality colonoscopy in the past 3 years, or 3. Individuals who have a personal history of colon polyps 2. Willing and able to provide written informed consent for study participation 3. Willing to consume 2 ounces (56 grams) of walnuts daily for 3 weeks 4. Willing to avoid intake of EA/ET-rich foods and beverages (e.g., pomegranates, hazelnuts, pistachios, strawberries, raspberries, blackberries, oak-aged wines, and other items on a list given by researchers) and fermented dairy products containing viable Bifidobacteria or Lactobacilli) 5. Willing to stop taking dietary supplements, including probiotics 6. Willing to have two separate blood draws, as well as urine and stool collections 7. Willingness to comply with all study requirements
Exclusion criteria
1. Individual has a personal history of CRC, or a history of any malignancy (other than skin cancer) within the past 5 years 2. Individual meets the Amsterdam criteria for Lynch Syndrome or has a history of familial adenomatous polyposis (FAP) 3. Individual has been treated with immunosuppressive agents or systemic steroids, excluding inhalers, at least two weeks prior to the Screening Visit and for the duration of the study 4. Use of antibiotics at least one month prior to the Screening Visit and for the duration of the study 5. Patients with severe medical illness or those at high risk for anesthesia, as determined by good clinical practice 6. Current evidence or previous history of ulcerative colitis or Crohn's disease 7. Colonoscopy performed for reasons other than screening or surveillance for CRC 8. HIV infection, chronic viral hepatitis 9. Allergy to walnuts or hypersensitivity to tree nuts 10. Peri-menopausal women with any chance or plan of pregnancy 11. Individuals with blood coagulation disorders or on anti-coagulant therapy 12. Any other condition that, in the opinion of the PI, might interfere with study objectives 13. No race/ethnicity, language or gender exclusions for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Association of urolithin levels with the immune composition of the tumor microenvironment | Day 30 | FFPE colon polyp tissue sections will be analyzed by the NCI Imaging Core (Frederick, MD) using imaging mass cytometry (IMC) to determine immune cell populations present within the tumor microenvironment. This data will be used to establish correlations with urolithin production. |
| Bacterial diversity changes and strain-level variations in the fecal microbiome | Day 7 and Day 28 | Bacterial diversity/abundance changes and strain-level variations in the fecal microbiome will be assessed using metagenomic shotgun sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation). |
| Bacterial gene expression profile changes in the fecal microbiome | Day 7 and Day 28 | Bacterial gene expression profile changes in the fecal microbiome will be assessed using metagenomic ribonucleic acid (RNA) sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation). |
| Urolithin levels in urine | Day 0, Day 7 and Day 30 | Urolithin levels will be measured in urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry at day 0 (baseline/pre-washout), day 7 (post-washout/pre-walnut supplementation) and day 30 (post-walnut supplementation/end of study). |
| Association of urolithin levels with presence (and type) of colonic lesions | Day 30 | Baseline urolithin levels measured in the urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry will be associated with the presence (and type) of colonic lesions (e.g., advanced adenomas (AAs) or sessile serrated adenomas/polyps (SSA/Ps)) detected during the colonoscopy procedure at the end of the study (day 30). |
| Correlation of urolithin levels with fecal microbiome composition | Day 7 and Day 28 | Detailed statistical analyses will be used to correlate urolithin formation with the composition of the fecal microbiome at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation). |
| Correlation of colonic lesion gene expression with urolithin production | Day 30 | Colonic lesion (AAs and SSA/Ps) biopsies obtained at the end of the study (day 30) during the colonoscopy procedure will undergo DNA sequence-based analysis to determine gene expression profiling. These results will be compared to urinary urolithin levels measured at baseline to establish correlations between urolithin production and colorectal cancer risk markers. |
| Bacterial composition and taxonomy changes in the fecal microbiome | Day 7 and Day 28 | Bacterial composition and taxonomy changes in the fecal microbiome will be assessed using 16 Svedberg unit (16S) ribosomal ribonucleic acid (rRNA) sequencing, at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bile acid metabolism in stool | Day 7 and Day 30 | Primary and secondary bile acids in freeze-dried stool samples will be analyzed using standard liquid chromatography-mass spectrometry methods at day 7 (post-washout/pre-walnut supplementation) and at day 30 (post-walnut supplementation). |
| Inflammatory markers in blood | Day 7 and Day 30 | Markers of systemic inflammation associated with adenoma risk will be measured in plasma using commercial enzyme-linked immunoassay (ELISA) kits at day 7 (post-washout/pre-walnut supplementation) and at day 30 (end of study). |
| Correlation of dietary behavior with presence (or absence) of colonic polyps | Day 7 and Day 30 | Overall diet quality and habits documented on brief food questionnaires will be analyzed by NutritionQuest at day 7 (post-washout/pre-walnut supplementation). Dietary behavior data will be correlated with the presence or absence of colonic polyps detected during the colonoscopy procedure at the end of the study (day 30). |
| Correlation of dietary behavior with fecal microbiome composition and diversity | Day 7 and Day 30 | Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with fecal microbiome composition and diversity at day 7 (post-washout/pre-walnut supplementation) and at day 30 (post-walnut supplementation). |
| Correlation of dietary behavior with urolithin production | Day 7 and Day 30 | Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with urolithin levels at day 7 (post-washout/pre-walnut supplementation) and at day 30 (post-walnut supplementation). |
| Short-chain fatty acid composition in stool | Day 7 and Day 30 | Short-chain fatty acids in freeze-dried stool samples will be measured using differential mobility separation at day 7 (post-washout/pre-walnut supplementation) and at day 30 (post-walnut supplementation). |
Countries
United States
Contacts
Primary ContactAmy Pallotti
Backup ContactSlawa Gajewska
Outcome results
None listed