Pigs, unlike mice, have two distinct colonic stem cell populations similar to humans that respond to high-calorie diet prior to insulin resistance

Venkata Charepalli, Lavanya Reddivari, Sridhar Radhakrishnan, Elisabeth Eriksson, Xia Xiao, Sung Woo Kim, Frank Shen, Matam Vijay-Kumar, Qunhua Li, Vadiraja B. Bhat, Rob Knight, Jairam K.P. Vanamala

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HCD (23% fat) for 13 weeks. HCD- and SD-consuming pigs had similar total calorie intake, serum iron, insulin, and glucose levels. However, HCD elevated both colonic proliferative zone (KI-67) and stem cell zone (ASCL-2 and BMI-1). Proliferative zone correlated with elevated innate colonic inflammatory markers TLR-4, NF-κB, IL6, and lipocalin-2 (r ≥ 0.62, P = 0.02). Elevated gut bacterial phyla proteobacteria and firmicutes in HCD-consuming pigs correlated with proliferative and stem cell zone. Colonic proteome data revealed the upregulation of proteins involved in cell migration and proliferation and correlated with proliferative and stem cell zone expansion. Our study suggests that pig colon, unlike mice, has two distinct stem cells (ASCL-2 and BMI-1) similar to humans, and HCD increases expansion of colonic proliferative and stem cell zone. Thus, pig model can aid in the development of preventive strategies against gut bacterial dysbiosis and inflammation-promoted diseases, such as colon cancer.

Original languageEnglish (US)
Pages (from-to)442-450
Number of pages9
JournalCancer Prevention Research
Volume10
Issue number8
DOIs
StatePublished - Aug 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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