D-methionine alleviates cisplatin-induced mucositis by restoring the gut microbiota structure and improving intestinal inflammation
| Autor: | Cheng-Hsi Wu, Jiunn-Liang Ko, Jiuan-Miaw Liao, Shiang-Suo Huang, Meei-Yn Lin, Ling-Hui Lee, Li-Yu Chang, Chu-Chyn Ou |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Therapeutic Advances in Medical Oncology, Vol 11 (2019) |
| Druh dokumentu: | article |
| ISSN: | 1758-8359 17588359 |
| DOI: | 10.1177/1758835918821021 |
| Popis: | Background: There are close links between chemotherapy-induced intestinal mucositis and microbiota dysbiosis. Previous studies indicated that D-methionine was an excellent candidate for a chemopreventive agent. Here, we investigated the effects of D-methionine on cisplatin-induced mucositis. Materials and methods: Male Wistar rats (176–200 g, 6 weeks old) were given cisplatin (5 mg/kg) and treated with D-methionine (300 mg/kg). Histopathological, digestive enzymes activity, oxidative/antioxidant status, proinflammatory/anti-inflammatory cytokines in intestinal tissues were measured. Next-generation sequencing technologies were also performed to investigate the gut microbial ecology. Results: D-methionine administration increased villus length and crypt depth and improved digestive enzyme (leucine aminopeptidase, sucrose and alkaline phosphatase) activities in the brush-border membrane of cisplatin-treated rats ( p < 0.05). Furthermore, D-methionine significantly attenuated oxidative stress and inflammatory reaction and increased interleukin-10 levels in cisplatin-induced intestinal mucositis ( p < 0.05). Cisplatin administration resulted in high relative abundances of Deferribacteres and Proteobacteria and a low diversity of the microbiota when compared with control groups, D-methionine only and cisplatin plus D-methionine. Cisplatin markedly increased comparative abundances of Bacteroides caccae, Escherichia coli, Mucispirillum schaedleri, Bacteroides uniformis and Desulfovibrio C21-c20 , while Lactobacillus was almost completely depleted, compared with the control group. There were higher abundances of Lactobacillus , Lachnospiraceae, and Clostridium butyrium in cisplatin plus D-methionine rats than in cisplatin rats. D-methionine treatment alone significantly increased the number of Lactobacillus reuteri . Conclusion: D-methionine protects against cisplatin-induced intestinal damage through antioxidative and anti-inflammatory effects. By enhancing growth of beneficial bacteria (Lachnospiraceae and Lactobacillus ), D-methionine attenuates gut microbiome imbalance caused by cisplatin and maintains gut homeostasis. |
| Databáze: | Directory of Open Access Journals |
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