| Background: Diet, lifestyle factors and recently, the gut microbiome, have been considered important for colorectal cancer. However, for some dietary factors, such as coffee and tea, the epidemiological evidence is inconclusive. It also remains unclear what are the personal factors that may help shape the gut microbiome and what are suitable methods of fecal biospecimen collection for large-scale epidemiological study of these microbial communities.;Objective: To better understand the relationships between diet and colorectal cancer; diet, lifestyle factors and gut microbiome; and fecal collection methods for study of the human gut microbiome.;Methods: To study the relationship between diet and colorectal cancer, I prospectively examined the association between coffee and tea intake with colorectal cancer risk in 57,398 men and women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. To better understand which dietary and lifestyle factors may be important for modifying the human gut microbiome, I assessed microbial global diversity and specific taxon abundances according to sex, body mass index (BMI), and dietary fiber intake in 82 control group participants. To evaluate whether different fecal collection and storage methods impact gut microbiome diversity parameters, I compared gut microbiome overall diversity and specific taxon abundances according to collection of fecal samples on Hemoccult Sensa RTM cards, in standard Eppendorf tubes at room temperature and at -80°C, and in RNAlater among three healthy volunteers.;Results: In my study of diet and colorectal cancer, I did not find that greater coffee intake and tea intake were associated with risk of colorectal cancer (p=0.23 and p=0.17, respectively). In my study of the personal determinants of the gut microbiome, I found that sex (women vs. men, p=0.001) and BMI (>25 kg/m2 vs. <25 kg/m2, p=0.05) were associated with gut microbiome diversity. Dietary fiber from fruits and vegetables and from beans was positively associated with Clostridia (p=0.009) and Actinobacteria (p=0.006) abundances, respectively. When I evaluated the gut microbiome according to fecal biospecimen collection method, I found that microbiome structure (p=0.497) and relative abundance of major microbial phyla (p>0.05) did not differ significantly by collection method.;Conclusions: Overall, my findings do not support a beneficial relationship between the dietary factors, coffee and tea, and colorectal cancer risk; however, my findings do support a role for the human gut microbiome as a possible therapeutic target by modification of dietary and lifestyle factors. Furthermore, my findings point to the potential use of fecal occult blood test cards for fecal biospecimen collection in large-scale studies of the gut microbiome. Future, large-scale epidemiological studies incorporating traditional diet and lifestyle factors with assessments of the gut microbiome and colorectal cancer will further delineate the complexity of the colorectal cancer pathway and has implications for targeted prevention of colorectal tumors. |