Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Microbiol Spectr. 2023 Jun 15;11(3):e0313022. doi: 10.1128/spectrum.03130-22. Epub 2023 May 22.
Cachexia is a lethal muscle-wasting syndrome associated with cancer and chemotherapy use. Mounting evidence suggests a correlation between cachexia and intestinal microbiota, but there is presently no effective treatment for cachexia. Whether the Ganoderma lucidum polysaccharide Liz-H exerts protective effects on cachexia and gut microbiota dysbiosis induced by the combination cisplatin plus docetaxel (cisplatin + docetaxel) was investigated. C57BL/6J mice were intraperitoneally injected with cisplatin + docetaxel, with or without oral administration of Liz-H. Body weight, food consumption, complete blood count, blood biochemistry, and muscle atrophy were measured. Next-generation sequencing was also performed to investigate changes to gut microbial ecology. Liz-H administration alleviated the cisplatin + docetaxel-induced weight loss, muscle atrophy, and neutropenia. Furthermore, upregulation of muscle protein degradation-related genes ( and ) and decline of myogenic factors (MyoD and myogenin) after treatment of cisplatin and docetaxel were prevented by Liz-H. Cisplatin and docetaxel treatment resulted in reducing comparative abundances of and , but Liz-H treatment restored these to normal levels. This study indicates that Liz-H is a good chemoprotective reagent for cisplatin + docetaxel-induced cachexia. Cachexia is a multifactorial syndrome driven by metabolic dysregulation, anorexia, systemic inflammation, and insulin resistance. Approximately 80% of patients with advanced cancer have cachexia, and cachexia is the cause of death in 30% of cancer patients. Nutritional supplementation has not been shown to reverse cachexia progression. Thus, developing strategies to prevent and/or reverse cachexia is urgent. Polysaccharide is a major biologically active compound in the fungus Ganoderma lucidum. This study is the first to report that polysaccharides could alleviate chemotherapy-induced cachexia via reducing expression of genes that are known to drive muscle wasting, such as and These results suggest that Liz-H is an effective treatment for cisplatin + docetaxel-induced cachexia.
恶病质是一种与癌症和化疗使用相关的致命性肌肉消耗综合征。越来越多的证据表明恶病质与肠道微生物群之间存在相关性，但目前尚无有效的恶病质治疗方法。本研究旨在探讨灵芝多糖 Liz-H 对顺铂加多西紫杉醇（顺铂+多西紫杉醇）联合诱导的恶病质和肠道微生物失调的保护作用。C57BL/6J 小鼠腹腔注射顺铂+多西紫杉醇，同时或不给予 Liz-H 口服治疗。测量体重、食物消耗、全血细胞计数、血液生化和肌肉萎缩。还进行了下一代测序以研究肠道微生物生态的变化。Liz-H 给药缓解了顺铂+多西紫杉醇引起的体重减轻、肌肉萎缩和中性粒细胞减少。此外，Liz-H 还防止了顺铂和多西紫杉醇处理后肌肉蛋白降解相关基因（和）的上调和肌生成因子（MyoD 和肌细胞生成素）的下降。顺铂和多西紫杉醇处理导致和的相对丰度降低，但 Liz-H 处理将其恢复到正常水平。这项研究表明，Liz-H 是顺铂+多西紫杉醇诱导恶病质的一种良好的化学保护试剂。恶病质是一种由代谢失调、厌食、全身炎症和胰岛素抵抗驱动的多因素综合征。大约 80%的晚期癌症患者患有恶病质，30%的癌症患者因恶病质而死亡。营养补充剂并未显示出可逆转恶病质进展。因此，迫切需要开发预防和/或逆转恶病质的策略。多糖是灵芝真菌中的一种主要生物活性化合物。这项研究首次报道，多糖可通过降低已知驱动肌肉消耗的基因（如和）的表达来缓解化疗引起的恶病质。这些结果表明 Liz-H 是治疗顺铂+多西紫杉醇诱导的恶病质的有效方法。
