Pan Pan1, Kiyoko Oshima2, Yi-Wen Huang3, Martha Yearsley4, Jianying Zhang5, Mark Arnold6, Jianhua Yu7, Li-Shu Wang1. 1. Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 2. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA. 3. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA. 4. Department of Pathology, The Ohio State University, Columbus, Ohio, USA. 5. Department of Science of Informatics, Division of Biostatistics, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA. 6. Department of Surgery, The Ohio State University, OH, USA. 7. Hematologic Malignancies and Stem Cell Transplantation Institute, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA.
Abstract
BACKGROUND: The gut microbiota plays a pivotal role in the development of inflammatory bowel disease and colorectal cancer. OBJECTIVE: To determine whether the gut microbiota is required for the chemoprotective effects of black raspberries (BRBs) in Apc Min/+ mice. METHODS: Apc Min/+ mice were given (a) a control diet for 8 weeks, or (b) the control diet for 4 weeks and then a 5% BRB diet for additional 4 weeks, or (c) the control diet and antibiotics for 4 weeks followed by the 5% BRB diet and antibiotics for the next 4 weeks. At the end of the study, all the mice were euthanized, and colonic and intestinal polyps were counted. mRNA expression levels of TLR4, NF-κB1, and COX2 were determined in colon and small intestine of these Apc Min/+ mice by quantitative real-time PCR. RESULTS: 5% BRBs significantly suppressed intestinal and colonic polyp development in the Apc Min/+ mice, whereas antibiotics significantly abolished BRBs' chemoprotective effects. BRBs decreased mRNA levels of TLR4, NF-κB1, and COX2 in colon, whereas significantly enhanced mRNA levels of TLR4 and NF-κB1 were observed in small intestine of BRB-treated Apc Min/+ mice fed antibiotics. CONCLUSIONS: The gut microbiota is required for BRBs' chemoprotection against polyp development in Apc Min/+ mice.
BACKGROUND: The gut microbiota plays a pivotal role in the development of inflammatory bowel disease and colorectal cancer. OBJECTIVE: To determine whether the gut microbiota is required for the chemoprotective effects of black raspberries (BRBs) in Apc Min/+ mice. METHODS:Apc Min/+ mice were given (a) a control diet for 8 weeks, or (b) the control diet for 4 weeks and then a 5% BRB diet for additional 4 weeks, or (c) the control diet and antibiotics for 4 weeks followed by the 5% BRB diet and antibiotics for the next 4 weeks. At the end of the study, all the mice were euthanized, and colonic and intestinal polyps were counted. mRNA expression levels of TLR4, NF-κB1, and COX2 were determined in colon and small intestine of these Apc Min/+ mice by quantitative real-time PCR. RESULTS: 5% BRBs significantly suppressed intestinal and colonic polyp development in the Apc Min/+ mice, whereas antibiotics significantly abolished BRBs' chemoprotective effects. BRBs decreased mRNA levels of TLR4, NF-κB1, and COX2 in colon, whereas significantly enhanced mRNA levels of TLR4 and NF-κB1 were observed in small intestine of BRB-treated Apc Min/+ mice fed antibiotics. CONCLUSIONS: The gut microbiota is required for BRBs' chemoprotection against polyp development in Apc Min/+ mice.
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Keywords:
ApcMin/+; Black raspberries; COX2; NF-κB; TLR4; antibiotics