Nature：艰难梭菌“剥削”宿主炎症反应中产生的代谢物
- ①在小鼠肠道中定植野生型艰难梭菌（Cd）和不产毒素的突变型Cd，其中野生型Cd引发更严重的炎症，伴随Cd的山梨醇代谢途径上调；
- ②Cd通过上调该途径来利用源自饮食和宿主产生的山梨醇作为养分，当山梨醇缺乏时，Cd的毒素表达升高；
- ③宿主通过醛糖还原酶将葡萄糖转化为山梨醇，该酶在多种肠道免疫细胞中表达，且在Cd感染等引发的炎症期间表达上调，参与宿主抗感染免疫应答；
- ④Cd产生毒素引发宿主炎症，从而诱导宿主生成更多山梨醇来为Cd所用。
主编推荐语
一些肠道病原体能通过引起宿主的病理和炎症反应，来获得特定的代谢优势，从而在与其他菌群成员的竞争中胜出。艰难梭菌产生的毒素能引起宿主肠炎，但这种病理状态如何令艰难梭菌获益尚不清楚。Nature最新发表的来自斯坦福大学Justin Sonnenburg团队的研究表明，艰难梭菌能利用山梨醇作为养分来生长，这种致病菌通过引发宿主炎症反应，来诱导宿主产生更多的山梨醇为其所用，从而令自身更好地在宿主肠道内定植。这些发现阐释了艰难梭菌利用宿主代谢物来获得代谢优势的机制，为研究治疗艰难梭菌感染的疗法带来新启示。
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C. difficile exploits a host metabolite produced during toxin-mediated disease
艰难梭菌利用在毒素介导的疾病中产生的一种宿主代谢物
10.1038/s41586-021-03502-6
2021-04-28, Article
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Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile is responsible for a toxin-mediated colitis that causes 450,000 infections and 15,000 deaths in the United States each year1; however, the molecular mechanisms by which C. difficile benefits from this pathology remain unclear. To understand how the metabolism of C. difficile adapts to the inflammatory conditions that its toxins induce, here we use RNA sequencing to define, in a mouse model, the metabolic states of wild-type C. difficile and of an isogenic mutant that lacks toxins. By combining bacterial and mouse genetics, we demonstrate that C. difficile uses sorbitol derived from both diet and host. Host-derived sorbitol is produced by the enzyme aldose reductase, which is expressed by diverse immune cells and is upregulated during inflammation—including during toxin-mediated disease induced by C. difficile. This work highlights a mechanism by which C. difficile can use a host-derived nutrient that is generated during toxin-induced disease by an enzyme that has not previously been associated with infection.
First Authors:
Kali M Pruss
Correspondence Authors:
Justin L Sonnenburg
All Authors:
Kali M Pruss,Justin L Sonnenburg
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