Seki Natsumi, Kimizuka Tatsuki, Gondo Monica, Yamaguchi Genki, Sugiura Yuki, Akiyama Masahiro, Yakabe Kyosuke, Uchiyama Jun, Higashi Seiichiro, Haneda Takeshi, Suematsu Makoto, Hase Koji, Kim Yun-Gi
Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan.
Department of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan.
iScience. 2022 Aug 3;25(8):104838. doi: 10.1016/j.isci.2022.104838. eCollection 2022 Aug 19.
-Amino acids (-AAs) have various functions in mammals and microbes. -AAs are produced by gut microbiota and can act as potent bactericidal molecules. Thus, -AAs regulate the ecological niche of the intestine; however, the actual impacts of -AAs in the gut remain unknown. In this study, we show that -Tryptophan (-Trp) inhibits the growth of enteric pathogen and colitogenic pathobionts. The growth of is strongly inhibited by -Trp treatment. Moreover, -Trp protects mice from lethal . infection via reduction of the pathogen. Additionally, -Trp prevents the development of experimental colitis by the depletion of specific microbes in the intestine. -Trp increases the intracellular level of indole acrylic acid (IA), a key molecule that determines the susceptibility of enteric microbes to -Trp. Treatment with IA improves the survival of mice infected with . . Hence, -Trp could act as a gut environmental modulator that regulates intestinal homeostasis.
-氨基酸(-AAs)在哺乳动物和微生物中具有多种功能。-AAs由肠道微生物群产生,可作为强效杀菌分子。因此,-AAs调节肠道的生态位;然而,-AAs在肠道中的实际影响仍不清楚。在本研究中,我们表明-色氨酸(-Trp)抑制肠道病原体和致结肠炎致病共生菌的生长。-Trp处理强烈抑制其生长。此外,-Trp通过减少病原体保护小鼠免受致死性的感染。此外,-Trp通过消耗肠道中的特定微生物来预防实验性结肠炎的发展。-Trp增加吲哚丙烯酸(IA)的细胞内水平,IA是决定肠道微生物对-Trp易感性的关键分子。用IA处理可提高感染的小鼠的存活率。因此,-Trp可作为调节肠道稳态的肠道环境调节剂。