Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasms

Inflammation

Colitis

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

All Drugs and Chemicals

Pomegranate

Raspberry

Cola

Strawberry

English Walnut

Blackberry

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.

Participants consume 2 ounces of walnuts daily for 21 days

Walnuts

Nuoxi Fan

Slawa Gajewska

Daniel W. Rosenberg, Ph.D.

John W. Birk, M.D.

Haleh Vaziri, M.D.

Thalia Matos

Steven M. Lipkin, M.D., Ph.D.

Felice Schnoll-Sussman, M.D.

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 29-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.

Walnuts and Colon Health

Microbiota, Metabolites and Colon Neoplasia

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).

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 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 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 29 (post-walnut supplementation/end of study).

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 adenoma/polyps (SSA/Ps)) detected during the colonoscopy procedure at the end of the study (day 29).

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).

Colonic lesion (AAs and SSA/Ps) biopsies obtained at the end of the study (day 29) 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.

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 28 (post-walnut supplementation).

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 28 (post-walnut supplementation).

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 29 (end of study).

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 29).

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 28 (post-walnut supplementation).

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 28 (post-walnut supplementation).

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

Professor of Medicine

Nutritional and Metabolic Diseases

Obesity

Malabsorption Syndromes

Syndrome

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Metabolic Diseases

Micronutrients

Iron

Trace Elements

A "Typical American" diet with "high" heme/non-heme iron" (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.

High heme iron diet

A "Typical American" diet with "low" heme/non-heme iron" (8 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.

Low iron diet

A plant-based diet with "high" non-heme iron" (18 mg total). Diet is isocaloric and has a macronutrient composition of total fat 35%, carbohydrates 50%, protein 15% of calories and fiber 9g/1000 calories. Subjects consumes the diet for 3 weeks with a minimum 3 week washout before the next diet.

Plant-based high non-heme iron diet

Lisa Tussing-Humphreys, PhD, MS, RD

Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity.

The investigator's objective is to conduct a crossover controlled feeding trial of: 1) a "Typical American" diet with "high" heme/non-heme iron", 2) a "Typical American" diet with "low" iron, and 3) a Mediterranean diet with "high" non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.

1. Typical American Diet with "high" heme/non-heme iron (16 mg)
2. Typical American Diet with "low" iron (8 mg)
3. Plant-based Diet with "high" non-heme iron (16 mg)

Obesity, Iron Regulation and Colorectal Cancer Risk

Fecal calprotectin, a proxy for colon tissue inflammation, will be measured from stool an calprotectin immunoassay

Circulating C-reactive protein, Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-a) will be measured from serum using immunoassays.

Stool samples to analyze the composition of the microbiota, extracted bacterial genomic DNA will be used as a template for polymerase chain reactions targeting the V4 variable regions of the 16S ribosomal ribonucleic acid gene. Amplicons generated from polymerase chain reaction will be run on the Illumina MiSeq sequencing platform to profile microbial communities at the phylum and genus level.

Serum hepcidin will be measured using an immunoassay

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Walnuts and Colon Health	NCT05195970	Colorectal Canc... Diet Habit	Walnuts	39 Years - 75 Years	UConn Health
Obesity, Iron Regulation and Colorectal Cancer Risk	NCT03548948	Colon Inflammat... Iron Malabsorpt... Obesity Diet Modificati...	High heme iron ... Low iron diet Plant-based hig...	55 Years - 70 Years	University of Illinois at Chicago

Spots Global Cancer Trial Database for colon inflammation