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2’-Fucosyllactose Ameliorates Chemotherapy-Induced Intestinal Mucositis by Protecting Intestinal Epithelial Cells Against Apoptosis
- Source :
- Cellular and Molecular Gastroenterology and Hepatology, Cellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 2, Pp 441-457 (2022)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Background & Aims Intestinal mucositis, a severe complication of antineoplastic therapeutics, is characterized by mucosal injury and inflammation in the small intestine. Therapies for the prevention and treatment of this disease are needed. We investigated whether 2’-fucosyllactose (2’-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis. Methods A mouse small intestinal epithelial (MSIE) cell line, mouse enteroid cultures, and human gastrointestinal tumor cell lines (AGS and HT29) were co-treated with the chemotherapy agent 5-fluorouracil (5-FU) and 2’-FL. Mice were injected intraperitoneally with 5-FU to induce intestinal mucositis. 2’-FL was administered in the drinking water to mice before (pretreatment) or concurrently with 5-FU injection. Body weight and pathologic changes were analyzed. Results 2’-FL alleviated 5-FU inhibition of cell growth in MSIE cells, but not in AGS and HT29 cells. The 5-FU–induced apoptosis in MSIE cells and enteroids was suppressed by 2’-FL. Compared with 5-FU treatment alone, 2’-FL pretreatment protected against body weight loss, and ameliorated inflammation scores, proinflammatory cytokine production, shortening of villi, epithelial cell apoptosis, goblet cell loss, and tight junctional complex disruption in the small intestine. 2’-FL concurrent treatment had less of an effect on intestinal mucositis than 2’-FL pretreatment. Interestingly, no effect of 2’-FL was observed on 5-FU–induced S-phase arrest in MSIE, AGS, and HT29 cells. Neither pretreatment nor concurrent treatment with 2’-FL affected 5-FU–induced inhibition of proliferation in MSIE cells. Conclusions This study shows a novel direct effect of 2’-FL in protecting small intestinal epithelial cells against apoptosis stimulated by 5-FU, which may contribute to prevention of 5-FU–induced intestinal mucositis.<br />Graphical abstract
- Subjects :
- Proliferation
MSIE, mouse small intestine epithelial cells
MPO, myeloperoxidase
Apoptosis
RC799-869
IEC, intestinal epithelial cell
Mice
PCR, polymerase chain reaction
Human Milk Oligosaccharides
Original Research
TNF, tumor necrosis factor
Gastroenterology
ELISA, enzyme-linked immunosorbent assay
Diseases of the digestive system. Gastroenterology
2’-FL, 2’-fucosyllactose
mRNA, messenger RNA
medicine.anatomical_structure
LPS, lipopolysaccharide
FITC, fluorescein isothiocyanate
Fluorouracil
Goblet Cells
medicine.symptom
Diarrhea
Mucositis
Antimetabolites, Antineoplastic
5-Fluorouracil
EdU, 5-ethynyl-2'-deoxyuridine
PBS, phosphate-buffered saline
Inflammation
Proinflammatory cytokine
HT29 Cells
FBS, fetal bovine serum
medicine
Animals
HMO, human milk oligosaccharide
NMR, nuclear magnetic resonance
SV40, simian virus 40
ZO-1, Zona occludin-1
Goblet cell
Hepatology
Cell growth
business.industry
medicine.disease
Small intestine
IL, interleukin
Cancer research
5-FU, 5-fluorouracil
business
Trisaccharides
Intestinal Inflammation
Subjects
Details
- Language :
- English
- ISSN :
- 2352345X
- Volume :
- 13
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....cecb7b66e0a7213c576cf778eedd4f80