Exfoliome sequencing and 16SV4 sequencing for mice given bacteria engineered to produce serotonin. Mus musculus

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, Escherichia coli 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 the 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.

胃肠道菌群在肠道蠕动、内稳态维持以及功能异常调控中发挥关键作用。由于肠道细菌可产生或代谢种类繁多的代谢物，解析微生物影响宿主的机制面临诸多挑战。在此，我们阐述了对肠道共生菌大肠杆菌Nissle 1917（Escherichia coli Nissle 1917）的工程化改造，使其能够生物合成人类代谢物5-羟色胺（serotonin），以此探究微生物源生物胺对宿主生理的影响。将该工程菌经口给药给小鼠后，其可定植于大肠并产生5-羟色胺。接触产5-羟色胺工程菌的小鼠，其肠道在转录水平与生理层面均出现了生物学变化。本研究构建了一种利用工程菌调控肠腔5-羟色胺水平的全新框架，并提示改造型微生物疗法在治疗人类肠道疾病方面具备潜在临床应用价值。