Weiwei Cui, Meng Guo, Dong Liu, Peng Xiao, Chuancheng Yang, Haidi Huang, Chunhui Liang, Yinghong Yang, Xiaolong Fu, Yudan Zhang, Jiaxing Liu, Shuang Shi, Jingjing Cong, Zili Han, Yunfei Xu, Lutao Du, Chengqian Yin, Yongchun Zhang, Jinpeng Sun, Wei Gu, Renjie Chai, Shu Zhu, Bo Chu
The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10...
January 2, 2024: Nature Cell Biology