加强肠道屏障,改善白血病患者化疗预后
创作:Lexi 审核:Lexi 2020年09月14日
  • 评估急性髓系白血病(AML)患者诱导化疗(7 + 3方案)前、中、后的微生物群组成;
  • 化疗后患者所有血细胞减少,功能性肠上皮细胞团减少,血浆瓜氨酸水平降低,粪便微生物群的α-多样性和β-多样性均下降;
  • 野生型(WT)AML小鼠化疗后瓜氨酸水平下降,E. coli和肠球菌负荷增加,且伴随组织学损伤;
  • 相比WT小鼠,分泌重组蛋白以增强黏液层的转基因Tg222 AML小鼠化疗结束3天后,瓜氨酸水平更高,上皮愈合更快,可保持肠道菌群α-多样性。
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Lexi
诱导化疗(7 + 3方案)仍是治疗急性髓系白血病(AML)的金标准,但会引起肠道损伤,并导致血行感染(BSI)等多种并发症。最新发表在Gut Microbes的研究通过评估急性髓系白血病(AML)患者诱导化疗(7 + 3方案)前、中、后的微生物群组成,并使用转基因Tg222 AML小鼠模型模拟AML患者,评估小鼠化疗前后肠道菌群组成,发现加强肠道屏障是限制BSI和改善AML患者预后的潜在策略。
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Gut Microbes [IF:7.74]

Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening

强化化疗对急性髓系白血病肠道屏障和微生物群的影响及后果:粘膜强化的作用

10.1080/19490976.2020.1800897

2020-09-06, Article

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Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and β-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients’ outcome.

First Authors:
Thomas Hueso

Correspondence Authors:
David Seguy

All Authors:
Thomas Hueso,Kenneth Ekpe,Camille Mayeur,Anna Gatse,Marie Joncquel-Chevallier Curt,Guillaume Gricourt,Christophe Rodriguez,Charles Burdet,Guillaume Ulmann,Christel Neut,Salah-Eddine Amini,Patricia Lepage,Bruno Raynard,Christophe Willekens,Jean-Baptiste,Micol,Stéphane De Botton,Ibrahim Yakoub-Agha,Frédéric Gottrand,Jean-Luc Desseyn,Muriel Thomas,Paul-Louis Woerther,David Seguy

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