Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01CA252045-01A1 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
| Weill Medical College of Cornell University | OTHER |
| University of Connecticut |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Walnut Consumption | Experimental | Following enrollment, participants will start a 7-day wash-out period where they will be asked to avoid foods and beverages high in ellagitannins. These include pomegranates, hazelnuts, pistachios, walnuts (besides the samples given by the researchers), strawberries, raspberries, blackberries, oak-aged wines and spirits; a full list of foods and beverages to avoid will be provided. Then, participants will consume 2 ounces of walnuts daily with their usual diet while continuing to avoid ellagitannins for 21 days prior to their routine colonoscopy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Walnuts | Other | Participants consume 2 ounces of walnuts daily for 21 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Bacterial composition and taxonomy changes in the fecal microbiome | 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). | Day 7 and Day 28 |
| Bacterial diversity changes and strain-level variations in the fecal microbiome | 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). | Day 7 and Day 28 |
| Bacterial gene expression profile changes in the fecal microbiome | 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). | Day 7 and Day 28 |
| Urolithin levels in urine | 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). | Day 0, Day 7 and Day 30 |
| Association of urolithin levels with presence (and type) of colonic lesions | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Short-chain fatty acid composition in stool | 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). | Day 7 and Day 30 |
| Bile acid metabolism in stool |
Not provided
Inclusion Criteria:
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):
Willing and able to provide written informed consent for study participation
Willing to consume 2 ounces (56 grams) of walnuts daily for 3 weeks
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)
Willing to stop taking dietary supplements, including probiotics
Willing to have two separate blood draws, as well as urine and stool collections
Willingness to comply with all study requirements
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Daniel W. Rosenberg, Ph.D. | UConn Health | Principal Investigator |
| Christian Jobin, Ph.D. | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UConn Health | Farmington | Connecticut | 06032 | United States | ||
| Weill Cornell Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37237848 | Background | Fan N, Fusco JL, Rosenberg DW. Antioxidant and Anti-Inflammatory Properties of Walnut Constituents: Focus on Personalized Cancer Prevention and the Microbiome. Antioxidants (Basel). 2023 Apr 22;12(5):982. doi: 10.3390/antiox12050982. | |
| 39548408 | Background | Liu H, Birk JW, Provatas AA, Vaziri H, Fan N, Rosenberg DW, Gharaibeh RZ, Jobin C. Correlation between intestinal microbiota and urolithin metabolism in a human walnut dietary intervention. BMC Microbiol. 2024 Nov 15;24(1):476. doi: 10.1186/s12866-024-03626-5. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D005247 | Feeding Behavior |
| D003092 | Colitis |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| OTHER |
| California Walnut Commission | OTHER |
| Spanish National Research Council | OTHER_GOV |
| University of Florida | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
| Day 30 |
| Correlation of urolithin levels with fecal microbiome composition | 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). | Day 7 and Day 28 |
| Correlation of colonic lesion gene expression with urolithin production | 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. | Day 30 |
| Association of urolithin levels with the immune composition of the tumor microenvironment | 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. | 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). |
| Day 7 and Day 30 |
| Inflammatory markers in blood | 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). | Day 7 and Day 30 |
| Correlation of dietary behavior with presence (or absence) of colonic polyps | 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). | Day 7 and Day 30 |
| Correlation of dietary behavior with fecal microbiome composition and diversity | 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). | Day 7 and Day 30 |
| Correlation of dietary behavior with urolithin production | 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). | Day 7 and Day 30 |
| New York |
| New York |
| 10065 |
| United States |
| 39995164 | Background | Moussa MR, Fan N, Birk J, Provatas AA, Mehta P, Hatano Y, Chun OK, Darooghegi Mofrad M, Lotfi A, Aksenov A, Motta VN, Zenali M, Vaziri H, Grady JJ, Nakanishi M, Rosenberg DW. Systemic Inflammation and the Inflammatory Context of the Colonic Microenvironment Are Improved by Urolithin A. Cancer Prev Res (Phila). 2025 Apr 1;18(4):235-250. doi: 10.1158/1940-6207.CAPR-24-0383. |
| 31137456 | Background | Nakanishi M, Matz A, Klemashevich C, Rosenberg DW. Dietary Walnut Supplementation Alters Mucosal Metabolite Profiles During DSS-Induced Colonic Ulceration. Nutrients. 2019 May 20;11(5):1118. doi: 10.3390/nu11051118. |
| 31818852 | Background | Chen Y, Nakanishi M, Bautista EJ, Qendro V, Sodergren E, Rosenberg DW, Weinstock GM. Colon Cancer Prevention with Walnuts: A Longitudinal Study in Mice from the Perspective of a Gut Enterotype-like Cluster. Cancer Prev Res (Phila). 2020 Jan;13(1):15-24. doi: 10.1158/1940-6207.CAPR-19-0273. Epub 2019 Dec 9. |
| 27215566 | Background | Nakanishi M, Chen Y, Qendro V, Miyamoto S, Weinstock E, Weinstock GM, Rosenberg DW. Effects of Walnut Consumption on Colon Carcinogenesis and Microbial Community Structure. Cancer Prev Res (Phila). 2016 Aug;9(8):692-703. doi: 10.1158/1940-6207.CAPR-16-0026. Epub 2016 May 23. |
| 31754633 | Background | Hong BY, Ideta T, Lemos BS, Igarashi Y, Tan Y, DiSiena M, Mo A, Birk JW, Forouhar F, Devers TJ, Weinstock GM, Rosenberg DW. Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia. NPJ Precis Oncol. 2019 Nov 14;3:29. doi: 10.1038/s41698-019-0101-6. eCollection 2019. |
| 27158799 | Background | Tomas-Barberan FA, Gonzalez-Sarrias A, Garcia-Villalba R, Nunez-Sanchez MA, Selma MV, Garcia-Conesa MT, Espin JC. Urolithins, the rescue of "old" metabolites to understand a "new" concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201500901. Epub 2016 Jun 20. |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D001522 | Behavior, Animal |
| D001519 | Behavior |
| D005759 | Gastroenteritis |