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L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2024 May; Vol. 68 (9), pp. e2300704. Date of Electronic Publication: 2024 Apr 24. - Publication Year :
- 2024
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Abstract
- Scope: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU).<br />Methods and Results: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg <superscript>-1</superscript> ) or high (2 mg kg <superscript>-1</superscript> ) doses of L-Glutamine daily, with 5-FU (50 mg kg <superscript>-1</superscript> ) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa.<br />Conclusions: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.<br /> (© 2024 Wiley‐VCH GmbH.)
- Subjects :
- Animals
Mice, Inbred ICR
Male
Toll-Like Receptor 4 metabolism
NF-E2-Related Factor 2 metabolism
Dysbiosis chemically induced
Dysbiosis drug therapy
Mice
NF-kappa B metabolism
Oxidative Stress drug effects
TOR Serine-Threonine Kinases metabolism
Antimetabolites, Antineoplastic adverse effects
Heme Oxygenase-1 metabolism
Gastrointestinal Microbiome drug effects
Fluorouracil adverse effects
Glutamine pharmacology
Mucositis chemically induced
Mucositis drug therapy
Mucositis metabolism
Intestinal Mucosa drug effects
Intestinal Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 68
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 38656560
- Full Text :
- https://doi.org/10.1002/mnfr.202300704