Methods: Software
Fields: Biological Sciences, Health Science, Microbiology

Collaborators: David A. C. Beck (eScience & Chemical Engineering), Jisun Paik (Comparative Medicine), Lillian Maggio-Price (Comparative Medicine), Piper Treuting (Comparative Medicine), (Gastroenterology)

(A) Multidimensional scaling of OTU abundances from fecal transplant experiment with donors fed a control and high vitamin D diet. The single color data points (lower right corner) represent the two donor samples for the control and high vitamin-D diet. Triangle represents high vitamin D and circle represents control diet. The cyan and magenta indicate gender (male and female, respectively) while the inner color indicates time post fecal transplant in weeks as white, grey and black for one, two and four weeks respectively. As with the initial fecal transplant study, the samples diverge from the donors rapidly but begin to become more donor-like by week 4. There is a strong division between the two diets in post-transplant and an additional separation by gender. (B) Community complexity for fecal transplant with donors fed control and high vitamin-D diets. The donor samples for each diet are shown at week 0. There is no significant difference by gender, however, the microbiota from high vitamin-D diet appears to establish a more diverse bacterial community.

(A) Multidimensional scaling of OTU abundances from fecal transplant experiment with donors fed a control and high vitamin D diet. The single color data points (lower right corner) represent the two donor samples for the control and high vitamin-D diet. Triangle represents high vitamin D and circle represents control diet. The cyan and magenta indicate gender (male and female, respectively) while the inner color indicates time post fecal transplant in weeks as white, grey and black for one, two and four weeks respectively. As with the initial fecal transplant study, the samples diverge from the donors rapidly but begin to become more donor-like by week 4. There is a strong division between the two diets in post-transplant and an additional separation by gender. (B) Community complexity for fecal transplant with donors fed control and high vitamin-D diets. The donor samples for each diet are shown at week 0. There is no significant difference by gender, however, the microbiota from high vitamin-D diet appears to establish a more diverse bacterial community.

Inflammatory Bowel Disease (IBD) is associated with increased colon-cancer risk. It is not clear why ≈10% of chronic colitis patients get neoplastic progression, while the vast majority do not. The gut microbiome differs between healthy individuals and patients with IBD or colon cancer. We hypothesize that the microbiota play a role in the development of colitis-associated colon cancer (CAC). To address this, we will use the Smad3-/- mouse model of CAC, where approximately 40% of mice develop cancer after gut inflammation is triggered by bacteria. We previously noted that the gut microbiota of mice that develop cancer (progressors) differs from that of cancer-free mice (non-progressors). We will expand on these findings by testing Koch’s postulate: eg. by transferring fecal samples of mice with and without cancer into germ-free Smad3-/- mice and examining for cancer development. Next, we will evaluate the translational potential of these mice as a bio-indicator/avatars of CAC in humans. We will transfer mucosa-associated microbiota of IBD patients (progressors vs. non-progressors) into germ-free Smad3-/- mice and examine for neoplastic development. Our studies will address the causative role of microbiota on CAC, develop a potential bioassay for assessing CAC risk, and identify microbial targets to modulate incidence of CAC.

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