Mitigation of Dextran-Sodium-Sulfate-Induced Colitis in Mice through Oral Administration of Microbiome-Derived Inosine and Its Underlying Mechanisms.
Int J Mol Sci
; 24(18)2023 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-37762155
ABSTRACT
BACKGROUND:
Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD).METHODS:
This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms.RESULTS:
An inosine intervention effectively improved the clinical signs in colitis mice, suppressed inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1ß) by regulating the nuclear factor-kappa B (NF-κB) pathway, and elevated the activities of anti-oxidative enzymes (including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Additionally, the inosine intervention significantly elevated the expression of tight junction proteins (ZO-1, occudin, and claudin-1) in mice with colitis. High-throughput sequencing revealed that the inosine intervention also prevented gut microbiota disorder by increasing the abundance of beneficial bacteria (Lachnospiraceae NK4A136 group, Romboutsia, Marvinbryantia, Clostridium sensu stricto 1, and Bifidobacterium) and reducing the abundance of harmful bacteria (Pseudomonas, Acinetobacter, and Tyzzerella) in mice with colitis.CONCLUSIONS:
Inosine played a significant role in mitigating colitis-related intestinal barrier injury and could potentially be used for therapy in clinical practice.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Colite
/
Microbioma Gastrointestinal
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article