Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury,Cell Host & Microbe

当前位置： X-MOL 学术 › Cell Host Microbe › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-08-27 , DOI: 10.1016/j.chom.2024.07.026
Christopher J Anderson ₁ , Laura Boeckaerts ₂ , Priscilla Chin ₃ , Javier Burgoa Cardas ₂ , Wei Xie ₂ , Amanda Gonçalves ₄ , Gillian Blancke ₅ , Sam Benson ₃ , Sebastian Rogatti ₃ , Mariska S Simpson ₃ , Anna Davey ₃ , Sze Men Choi ₂ , Sandrien Desmet ₆ , Summer D Bushman ₇ , Geert Goeminne ₆ , Peter Vandenabeele ₂ , Mahesh S Desai ₇ , Lars Vereecke ₅ , Kodi S Ravichandran ₈

Affiliation

VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; VIB BioImaging Core, Ghent, Belgium.
VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
VIB Metabolomics Core, Ghent, Belgium.
Department of Infection and Immunity, Luxembourg Institute of Health, L-4354 Esch-sur-Alzette, Luxembourg.
VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Cytotoxic chemotherapies have devastating side effects, particularly within the gastrointestinal tract. Gastrointestinal toxicity includes the death and damage of the epithelium and an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whether dysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from both mammalian and bacterial perspectives, we uncover an intestinal epithelial cell death-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our data demonstrate that chemotherapy-induced epithelial cell apoptosis and the purine-containing metabolites released from dying cells drive the inter-kingdom transcriptional re-wiring of the Enterobacteriaceae, including fundamental shifts in bacterial respiration and promotion of purine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract. Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levels reverses dysbiosis and improves intestinal recovery. These findings suggest that supportive therapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolving intestinal disease.

中文翻译：

基于代谢物的王国间通讯控制化疗损伤后肠道组织恢复

细胞毒性化疗具有毁灭性的副作用，尤其是在胃肠道内。胃肠道毒性包括上皮细胞的死亡和损伤以及肠道微生物群的失衡，也称为菌群失调。生态失调是否是组织毒性的直接因素是一个关键关注领域。在这里，从哺乳动物和细菌的角度，我们揭示了一个助长菌群失调的肠上皮细胞死亡-肠杆菌科信号轴。具体来说，我们的数据表明，化疗诱导的上皮细胞凋亡和垂死细胞释放的含嘌呤代谢物驱动肠杆菌科的界间转录重新布线，包括细菌呼吸的根本转变和嘌呤利用依赖性扩增的促进，这反过来又延迟了肠道的恢复。抑制上皮细胞死亡或将肠杆菌科限制在稳态水平可逆转菌群失调并改善肠道恢复。这些发现表明，维持肠杆菌科稳态水平的支持疗法可能有助于解决肠道疾病。

更新日期：2024-08-27

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南