肠道细菌代谢芳香族氨基酸生成多种循环代谢产物
Title：
A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Abstract：
The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.
All Authors：
Dylan Dodd,Matthew H Spitzer,William Van Treuren,Bryan D Merrill,Andrew J Hryckowian,Steven K Higginbottom,Anthony Le,Tina M Cowan,Garry P Nolan,Michael A Fischbach,Justin L Sonnenburg
First Authors：
Dylan Dodd
Correspondence：
Michael A Fischbach
内容要点：
本研究对产芽胞梭状芽胞杆菌代谢芳香族氨基酸的代谢通路进行遗传及代谢分析，该代谢通路可产生12种化合物，其中9种可在宿主血清中积累，有3种仅由细菌产生。 所有3种芳香族氨基酸（色氨酸、苯丙氨酸、酪氨酸）均可作为该代谢通路的底物。通过对产芽胞梭状芽胞杆菌进行遗传学修饰，并将其定殖于无菌小鼠体内，可调节这些代谢产物的血清水平，并影响肠道通透性及系统性炎症。未来或可通过调节肠道细菌的代谢通路治疗疾病。