Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.
Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.
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DOI：
10.1038/ismej.2015.209
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发表时间：
2016-06
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影响因子：
--
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中科院分区：
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--
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癌症恶病质是一种多因素综合征，包括肌肉萎缩和炎症。由于肠道微生物影响宿主免疫和代谢，我们研究了肠道微生物群在癌症和相关恶病质治疗管理中的作用。对两种癌症恶病质（急性白血病或结肠癌细胞皮下移植）小鼠模型的盲肠微生物组进行的全社区分析确定了常见的微生物特征，包括乳酸菌减少。肠杆菌科细菌和金氏副杆菌/ASF 519 也有所增加。根据这些信息，我们给白血病小鼠施用了含有菊粉型果聚糖和活罗伊氏乳杆菌 100-23 的合生元。这种治疗恢复了乳酸菌数量并降低了肠杆菌科细菌水平。它还可以减少肝癌细胞增殖、肌肉萎缩和发病率，并延长生存期。合生素的施用与控制肠道屏障功能和肠道免疫标志物的抗菌蛋白表达的恢复相关，但不影响能量需求的门静脉代谢组学印记。总之，这项研究提供的证据表明，肠道外癌症的发展可以影响肠道稳态和肠道微生物生态系统，而合生元干预通过针对肠道微生物群的某些改变，可以为宿主带来益处，延长生存期并减少癌症增殖和恶病质。
Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.
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影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1038/ismej.2014.45
发表时间：
2014-10
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
24.5
作者：
Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
通讯作者：
Delzenne NM
DOI：
10.1126/science.1224820
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arthur JC;Perez-Chanona E;Mühlbauer M;Tomkovich S;Uronis JM;Fan TJ;Campbell BJ;Abujamel T;Dogan B;Rogers AB;Rhodes JM;Stintzi A;Simpson KW;Hansen JJ;Keku TO;Fodor AA;Jobin C
通讯作者：
Jobin C
影响因子：
64.8
作者：
Claesson, Marcus J.;Jeffery, Ian B.;O'Toole, Paul W.
通讯作者：
O'Toole, Paul W.