The liver makes bile, an aqueous solution critical for fat absorption, which is secreted into the duodenum. Despite extensive studies on bile salts, other components of bile are less well characterized. Here we used global metabolomic analysis on bile from specific-pathogen-free, germ-free, Citrobacter rodentium-infected or Listeria monocytogenes-infected mice and identified a metabolome of 812 metabolites that were altered by both microbiota and enteric infection. Hepatic transcriptomics identified enteric-infection-triggered pathways that probably underlie bile remodelling. Enteric infection increased levels of four dicarboxylates in bile, including itaconate. Analysis of Acod1^−/− mice indicated that increased itaconate also increased tuft cell abundance, altered microbiota composition and function as detected by metagenomic analysis, and modulated host defence, leading to reduced Vibrio cholerae colonization. Our data suggest that enteric-infection-associated signals are relayed between the intestine and liver and induce transcriptional programmes that shape the bile metabolome, modifying the immunomodulatory and host defence functions of bile.

肝脏产生胆汁，这是一种对脂肪吸收至关重要的水溶液，胆汁分泌到十二指肠中。尽管对胆盐进行了广泛的研究，但胆汁的其他成分的表征不太明确。在这里，我们对来自无特定病原体、无细菌、啮齿动物柠檬酸杆菌感染或单核细胞增生李斯特菌感染小鼠的胆汁进行了整体代谢组学分析，并确定了 812 种代谢物的代谢组，这些代谢物被微生物群和肠道感染改变了。肝脏转录组学确定了可能是胆汁重塑基础的肠道感染触发途径。肠道感染增加了胆汁中四种二羧酸盐的水平，包括衣康酸盐。对 Acod1 ^{- / -} 小鼠的分析表明，衣康酸盐的增加还增加了簇状细胞的丰度，改变了宏基因组分析检测到的微生物群组成和功能，并调节了宿主防御，导致霍乱弧菌定植减少。我们的数据表明，肠道感染相关信号在肠道和肝脏之间传递，并诱导塑造胆汁代谢组的转录程序，从而改变胆汁的免疫调节和宿主防御功能。