结直肠癌（CRC）是由基因组的改变与膳食影响共同驱动的，其中肠道菌群被认为是疾病发展和进展的执行者。虽然荟萃分析揭示了CRC患者的机制细节，但研究异质性限制了因果关联。通过对遗传控制的小鼠队列进行多组学研究，我们发现饮食是微生物组和代谢组差异的主要驱动因素，高脂饮食（HFD）喂养的小鼠中α多样性降低，并且小鼠盲肠代谢物普遍发生变化。此外，胆酸胆酸的非经典氨基酸共轭（AA-CA）在HFD中增加。我们展示了AA-CA对肠道干细胞生长的影响，并且证明了Ileibacterium valens和Ruminococcus gnavus能够合成这些AA-CA。这个多组学数据集揭示了饮食引起的微生物组和代谢组的变化与疾病进展相关，并在未来诊断和治疗的发展中具有潜在的实用价值。版权所有 © 2023 作者。由Elsevier Inc.出版，版权所有。

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.