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.

通过诱导宿主病理和炎症，几种肠道病原体可以获得优于微生物群其他成员的特定代谢优势。病原体艰难梭菌是毒素介导的结肠炎的罪魁祸首，每年在美国造成 450,000 例感染和 15,000 例死亡¹；然而，艰难梭菌从这种病理学中获益的分子机制仍不清楚。为了解艰难梭菌的代谢如何适应其毒素诱导的炎症条件，我们在此使用 RNA 测序在小鼠模型中定义野生型艰难梭菌的代谢状态以及缺乏毒素的等基因突变体。通过结合细菌和小鼠遗传学，我们证明艰难梭菌使用来自饮食和宿主的山梨糖醇。宿主来源的山梨糖醇由醛糖还原酶产生，该酶由多种免疫细胞表达，并在炎症期间上调——包括在艰难梭菌诱导的毒素介导的疾病期间。这项工作突出了一种机制，艰难梭菌可以利用这种机制利用一种宿主衍生的营养素，这种营养素是在毒素诱发疾病期间由一种以前与感染无关的酶产生的。