Ellagic Acid, Urolithin and Colonic Microbial Communities Affected by Walnut Consumption
Condition: Colo-rectal Cancer; Colon Cancer; Diet Habit
MeSH terms: Rectal Neoplasms; Colonic Neoplasms
Study type: Interventional

Summary: 
      Briefly, this is a 28-day dietary intervention study participants will be asked to eat 2
      ounces (52 grams) of walnuts every day for 3 weeks, and at the end of the study period they
      will come in for a colonoscopy. Participants will first start a 1-week run-in period where
      they will be asked to avoid foods high in ellagic acid. In addition, they will be asked to
      complete food surveys and two sets of 3-day dietary records, and to provide colon biopsies
      for this study during their routine colonoscopy, as well as a blood, and two urine and stool
      samples. Urine samples will be used for analysis of urolithin, ellagic acid metabolites.
      Stool samples will be used to assess gut microbiota changes after walnut consumption. Dietary
      records will be used for compliance and Food Frequency Questionnaire will be used to assess
      dietary habits. Lastly, the biopsy samples will be used for analysis of biomarkers and
      anti-inflammatory in the colon, as well as adherent microbiome to the colonic tissue. Data
      will be analyzed based on the urolithin phenotypes.
    

Detailed description: 
      The investigators propose to address the influence of ellagic acid obtained from walnuts and
      its microbial-derived metabolites (urolithin) on the gut microbiome and inflammation-related
      biomarkers in a human clinical study. Patients will be enrolled and detailed demographic and
      dietary information, biopsy specimens through colonoscopies, as well as fecal, blood and
      urine samples will be collected. The wide range of gut urolithin levels provides the
      rationale for our proposed studies. Will the specific urolithin phenotypes show a disparate
      range of chemopreventive (anti-inflammatory) response to walnut consumption? The hypothesis
      is that walnut ingestion in "Phenotype A" participants (producing the highest levels of
      urolithin) will be associated with a beneficial anti-inflammatory response as tested in
      colonic mucosa and a higher abundance of bacterial species associated with ellagic acid
      metabolism. Although 16S ribosomal ribonucleic acid gene (rRNA) sequencing allows inexpensive
      bacterial identification at the genus/species level, a whole genome sequencing (mWGS) will be
      employed to achieve finer classification (strain level), and identify other microbes (e.g.,
      viruses, fungi, small eukaryotes). Furthermore, mWGS targets the entire genome of each
      microbe (not just the 16S rRNA gene), allowing for construction of a microbial gene
      catalogue, including a metabolic pathway description for each sample. This will characterize
      the functional potential of the microbial community. Ultimately, the proposed studies will
      inform the application of prebiotic to enhance the formation of urolithin metabolites from
      ellagic acid for the prevention of inflammation-associated Colorectal Cancer, a development
      that would have significant translational implications.
    

Intervention name(s): Walnuts
Intervention type(s): Other
Intervention description(s): Participants will consume 2 ounces of walnuts for 21 days
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Colorectal cancer; Microbiome; Urolithins; Walnuts