The Food Environment, Microbial Cysteine Metabolism, and Cancer Disparities

Not Applicable

Recruiting

• Conditions: Colorectal Cancer Risk; Colorectal Cancer Prevention; Colorectal Cancer; Diet Modification; Dietary Intervention; Cancer Prevention

• Registration Number: NCT07086833
• Lead Sponsor: Purdue University

Brief Summary

The goal of this clinical trial is to learn if changing cysteine levels in the diet can influence how the body processes cysteine in Black and White individuals aged 45-75 with a history of non-cancerous polyps. The main questions it aims to answer are:

* At the beginning of the study, do Black participants have higher levels of cortisol (a stress hormone) and compounds made from cysteine in their blood when compared to White participants?

* Does eating less cysteine lower the body's natural cysteine activity and lead to less gut bacteria that break down cysteine?

* Does eating less cysteine lead to less inflammation in the gut and lower levels of markers of inflammation in the blood?

Research will compare a high cysteine diet and a low cysteine diet, and each participant will eat both diets.

Participants will be in the study for 11 weeks and 2 days. Over the course of the study, participants will:

* Eat a high cysteine diet for 3 weeks, and a low cysteine diet for 3 weeks

* Eat a moderate cysteine diet for 1 week before each study diet

* Complete surveys

* Provide blood, stool, and saliva samples

* Maintain food logs

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-07-17
• Study First Submitted QC: 2025-07-17
• Last Update Submitted: 2025-07-17
• Study First Posted: 2025-07-25
• Last Update Posted: 2025-07-25
• Study Start: 2025-07-30
• Primary Completion: 2027-06-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Aged 45-75
• Up to date with CRC screening colonoscopy with a high risk of CRC, defined as a history of 3 or more adenomatous polyps (APs) or an AP >1 cm in the past 5 years
• Identify as Black or Non-Hispanic White
• If female, no menstrual period for at least six months
• Willingness to donate oral wash and stool samples
• Willingness to complete 24-hour dietary recalls

Exclusion Criteria

• Antibiotic use within the last 6 months
• Abnormal gastrointestinal transit
• A history of organ transplantation
• Use of illicit drugs, combustible tobacco, or dietary supplements
• Pre- or probiotics within the last two months
• A history of cancer treatment within the past 12 months
• CRC or a genetic predisposition to CRC
• A baseline body weight > 450 lbs
• Weight gain or loss > 4 kg 3 months prior to study
• Significant food allergies, food preferences or therapeutic or vegetarian diets
• Menstrual cycle within the last 6 months
• Antibiotics in the last 2 months
• Cannot keep a food record for 7 consecutive days during screening after detailed instruction
• Significant medical conditions
• History of eating disorders
• Alcoholism
• Individuals under the age of 18

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Colonic inflammation	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)	Fecal calprotectin, a marker of intestinal inflammation, will be measured from 100 mg of stool collected at the respective timeframe using a CALPRO Calprotectin ELISA test.
Fecal microbial content	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)	Microbial genomic DNA will be extracted from stool obtained at the respective timeframe using a Qiagen DNeasy PowerSoil Kit. Genomic DNA will be fragmented using a Covaris S2 and processed into libraries using an Integrated DNA Technologies xGen DNA Library Prep Kit. Final libraries will be pooled and sequenced on an Illumina NovaSeq X using 25B chemistry.
Systemic markers of inflammation	Baseline, Week 1 (Day 9), Week 2 (Day 16), Week 3 (Day 23), Week 4 (Day 30), Week 7 (Day 50), Week 8 (Day 58), Week 9 (Day 65), Week 11 (Day 79)	Serum from blood collected at the respective timeframe will be analyzed in triplicate with the Bio-Plex® Precision Pro™ (Bio rad, Hercules, CA) human cytokine 10-plex immunoassay to detect IL-1β, IL-6, IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-10, IL-12 (p70) and IL-13.

Secondary Outcome Measures

Name	Time	Method
Quantification of serum hydroxycortisol and cysteine metabolism markers	Baseline, Week 1 (Day 9), Week 2 (Day 16), Week 3 (Day 23), Week 4 (Day 30), Week 7 (Day 50), Week 8 (Day 58), Week 9 (Day 65), Week 11 (Day 79)	Serum hydroxycortisol and measures of cysteine metabolism (cysteine, homocysteine, lanthionine, cystathionine, serine) will be determined using hydrophilic interaction liquid chromatography with triple quadrupole tandem mass spectrometry by the Purdue Metabolite Profiling Facility.
Absolute and relative quantification of microbial cysteine metabolic genes	Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 7 (Day 49), Week 8 (Day 57), Week 9 (Day 64), Week 11 (Day 78)	Microbial genomic DNA will be extracted from stool obtained at the respective timeframe using a Qiagen DNeasy PowerSoil Kit. To estimate gene content, metagenomic libraries will be constructed from stool DNA. Metagenomic data will be processed to filter potential host DNA sequences and remove low-quality reads. Raw shotgun data will be assembled using MEGAHIT and assembled contigs will be binned using MetaBAT2. Taxonomic classification of binned contigs will be performed using CAT/BAT and differences genera that have functional genes for sulfur metabolism will be assessed. Assembled and binned metagenomes will be surveyed for genes for cysteine metabolism using custom hidden Markov model (HMM) libraries.
Whole body composition	Baseline, Week 4 (Day 30), Week 11 (Day 79)	DXA whole-body composition scan
Exfoliated intestinal epithelial cell transcriptomics	Baseline, Week 1 (Day 8), Week 4 (Day 29), Week 8 (Day 57), Week 11 (Day 78)	Exfoliated intestinal epithelial cells separated from stool collected at the respective timeframe with gene expression analysis

Trial Locations

Locations (2)

University Hospital Clinical Research Center; 🇺🇸 Indianapolis, Indiana, United States

Purdue Clinical Research Center; 🇺🇸 West Lafayette, Indiana, United States