A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide
A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide
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热量限制小鼠中更强大的肠道微生物群与化疗药物环磷酰胺引起的肠道损伤减轻有关
DOI：
10.1128/mbio.02903-18
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Zhang, Chenhong
中科院分区：
文献类型：
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作者：
Liu, Tao;Wu, Yanqiu;Zhang, Chenhong
环磷酰胺（CTX）广泛用于癌症化疗，但它经常引起粘膜炎，其中肠道微生物群的破坏可能起关键作用。肠道菌群的调控是否可以作为改善ctx诱导的粘膜炎的策略仍有待研究。在这里，我们观察了为期4周的卡路里限制（CR）对ctx诱导的粘膜炎的影响。与随意喂养的小鼠相比，CR小鼠对CTX的黏膜炎反应明显减轻，包括肠道通透性降低，细菌易位减少，上皮干细胞数量增加，上皮损伤减轻。CTX诱导了自由喂养对照小鼠肠道菌群的显著变化。相比之下，CR小鼠对CTX治疗的肠道微生物群没有显着变化。CR显著增加了肠道菌群中的乳酸菌和乳酸杆菌科菌群，这些菌群具有减轻炎症和改善肠道屏障功能的作用。这些发现表明，CR重塑的肠道微生物群更强健，可能有助于减轻环磷酰胺的副作用，这支持了癌症化疗将受益于针对肠道微生物群的策略的概念。通过限制卡路里来改善肠道菌群对人体健康有益。我们的研究结果显示，热量限制小鼠和自由喂养小鼠的反应不同。与随意喂养的小鼠相比，限制热量的小鼠对环磷酰胺副作用的敏感性较低，否则会观察到肠道完整性及其微生物群。这些结果显示了在癌症化疗前用CR控制肠道微生物群的潜在益处。
Cyclophosphamide (CTX) is widely used in cancer chemotherapy, but it often induces mucositis, in which the disruption of the gut microbiota might play a pivotal role. Whether the manipulation of the gut microbiota can be used as a strategy to improve CTX-induced mucositis remains to be studied. Here we observed the effects of a 4-week calorie restriction (CR) on CTX-induced mucositis. Compared with ad libitum-fed mice, CR mice showed significantly less mucositis in response to CTX, including lower intestinal permeability, less bacterial translocation, higher number of epithelial stem cells, and less epithelium damage. CTX induced significant shifts of the gut microbiota of the gut microbiota in ad libitum-fed control mice. In contrast, CR mice showed no significant change in their gut microbiota in responding to CTX treatment. CR significantly enriched the gut microbiota in Lactobacillus and Lachno-spiraceae which are known to mitigate inflammation and improve gut barrier function. These findings suggest that CR remodeled gut microbiota is more robust and may contribute to attenuate the side effects of cyclophosphamide, which supports the concept that cancer chemotherapy would benefit from strategies targeting the gut microbiota.IMPORTANCE Improving the gut microbiota via calorie restriction is beneficial for human health. Our findings showed differential responses between calorie-restricted mice and ad libitum-fed mice. Compared with the ad libitum-fed mice, the calorie-restricted mice were less susceptible to cyclophosphamide side effects otherwise observed on the gut integrity and its microbiota. These results show the potential benefits of manipulating the gut microbiota with CR prior to cancer chemotherapy.