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The Role of the Gut Microbiota in Colorectal Cancer Causation
Open AccessArticle

Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer

by Ching-Wei Chang 1,2,3,4,5, Hung-Chang Lee 3,4,5,6, Li-Hui Li 3, Jen-Shiu Chiang Chiau 3, Tsang-En Wang 2,4,5, Wei-Hung Chuang 7, Ming-Jen Chen 2,4,5, Horng-Yuan Wang 2,4,5, Shou-Chuan Shih 2,4,5, Chia-Yuan Liu 1,2,3,4,5,*,†, Tung-Hu Tsai 1,8,*,† and Yu-Jen Chen 1,3,4,5,9,*,†
1
Institute of Traditional Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
3
Department of Medical Research, MacKay Memorial Hospital, New Taipei City 25173, Taiwan
4
Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan
5
MacKay Junior College of Medicine, Nursing, and Management, New Taipei City 11260, Taiwan
6
MacKay Children’s Hospital, Taipei 10449, Taiwan
7
Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 11221, Taiwan
8
Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan
9
Department of Radiation Oncology, MacKay Memorial Hospital, Taipei 10449, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 386; https://doi.org/10.3390/ijms21020386
Received: 10 November 2019 / Revised: 18 December 2019 / Accepted: 6 January 2020 / Published: 8 January 2020
(This article belongs to the Special Issue The Role of the Dysbiotic Microbiota in Cancer)
FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells. View Full-Text
Keywords: FOLFOX; fecal microbiota transplant; intestinal mucositis; apoptosis; gut microbiota FOLFOX; fecal microbiota transplant; intestinal mucositis; apoptosis; gut microbiota
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Chang, C.-W.; Lee, H.-C.; Li, L.-H.; Chiang Chiau, J.-S.; Wang, T.-E.; Chuang, W.-H.; Chen, M.-J.; Wang, H.-Y.; Shih, S.-C.; Liu, C.-Y.; Tsai, T.-H.; Chen, Y.-J. Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer. Int. J. Mol. Sci. 2020, 21, 386.

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