Mavros Chrystal F, Bongers Mareike, Neergaard Frederik B F, Cusimano Frank, Sun Yiwei, Kaufman Andrew, Richardson Miles, Kammler Susanne, Kristensen Mette, Sommer Morten O A, Wang Harris H
Department of Systems Biology, Columbia University Irving Medical Center, New York, New York 10032, United States.
Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York 10032, United States.
ACS Synth Biol. 2024 Dec 20;13(12):4002-4014. doi: 10.1021/acssynbio.4c00453. Epub 2024 Nov 27.
Bacteria in the gastrointestinal tract play a crucial role in intestinal motility, homeostasis, and dysfunction. Unraveling the mechanisms by which microbes impact the host poses many challenges due to the extensive array of metabolites produced or metabolized by bacteria in the gut. Here, we describe the engineering of a gut commensal bacterium, Nissle 1917, to biosynthesize the human metabolite serotonin for examining the effects of microbially produced biogenic amines on host physiology. Upon oral administration to mice, our engineered bacteria reach the large intestine, where they produce serotonin. Mice treated with serotonin-producing bacteria exhibited biological changes in the gut at transcriptional and physiological levels. This work establishes a novel framework employing engineered bacteria to modulate luminal serotonin levels and suggests potential clinical applications of modified microbial therapeutics to address gut disorders in humans.
胃肠道中的细菌在肠道蠕动、体内平衡及功能紊乱中发挥着关键作用。由于肠道中细菌产生或代谢的代谢产物种类繁多，揭示微生物影响宿主的机制面临诸多挑战。在此，我们描述了对一种肠道共生细菌——1917年发现的嗜酸乳杆菌进行工程改造，使其生物合成人类代谢产物血清素，以研究微生物产生的生物胺对宿主生理的影响。给小鼠口服后，我们改造的细菌到达大肠并在那里产生血清素。用产生血清素的细菌处理的小鼠在转录和生理水平上肠道出现了生物学变化。这项工作建立了一个利用工程细菌调节肠腔血清素水平的新框架，并提出了改良微生物疗法在治疗人类肠道疾病方面的潜在临床应用。
