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

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Autores principales: Chang, Ching-Wei, Lee, Hung-Chang, Li, Li-Hui, Chiang Chiau, Jen-Shiu, Wang, Tsang-En, Chuang, Wei-Hung, Chen, Ming-Jen, Wang, Horng-Yuan, Shih, Shou-Chuan, Liu, Chia-Yuan, Tsai, Tung-Hu, Chen, Yu-Jen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013718/
https://www.ncbi.nlm.nih.gov/pubmed/31936237
http://dx.doi.org/10.3390/ijms21020386
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author Chang, Ching-Wei
Lee, Hung-Chang
Li, Li-Hui
Chiang Chiau, Jen-Shiu
Wang, Tsang-En
Chuang, Wei-Hung
Chen, Ming-Jen
Wang, Horng-Yuan
Shih, Shou-Chuan
Liu, Chia-Yuan
Tsai, Tung-Hu
Chen, Yu-Jen
author_facet Chang, Ching-Wei
Lee, Hung-Chang
Li, Li-Hui
Chiang Chiau, Jen-Shiu
Wang, Tsang-En
Chuang, Wei-Hung
Chen, Ming-Jen
Wang, Horng-Yuan
Shih, Shou-Chuan
Liu, Chia-Yuan
Tsai, Tung-Hu
Chen, Yu-Jen
author_sort Chang, Ching-Wei
collection PubMed
description 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.
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spelling pubmed-70137182020-03-09 Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer Chang, Ching-Wei Lee, Hung-Chang Li, Li-Hui Chiang Chiau, Jen-Shiu Wang, Tsang-En Chuang, Wei-Hung Chen, Ming-Jen Wang, Horng-Yuan Shih, Shou-Chuan Liu, Chia-Yuan Tsai, Tung-Hu Chen, Yu-Jen Int J Mol Sci Article 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. MDPI 2020-01-08 /pmc/articles/PMC7013718/ /pubmed/31936237 http://dx.doi.org/10.3390/ijms21020386 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Ching-Wei
Lee, Hung-Chang
Li, Li-Hui
Chiang Chiau, Jen-Shiu
Wang, Tsang-En
Chuang, Wei-Hung
Chen, Ming-Jen
Wang, Horng-Yuan
Shih, Shou-Chuan
Liu, Chia-Yuan
Tsai, Tung-Hu
Chen, Yu-Jen
Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title_full Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title_fullStr Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title_full_unstemmed Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title_short Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer
title_sort fecal microbiota transplantation prevents intestinal injury, upregulation of toll-like receptors, and 5-fluorouracil/oxaliplatin-induced toxicity in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013718/
https://www.ncbi.nlm.nih.gov/pubmed/31936237
http://dx.doi.org/10.3390/ijms21020386
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