Bacteria Engineered to Produce Serotonin Modulate Host Intestinal Physiology.

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2024-11-27 DOI:10.1021/acssynbio.4c00453

Chrystal F Mavros, Mareike Bongers, Frederik B F Neergaard, Frank Cusimano, Yiwei Sun, Andrew Kaufman, Miles Richardson, Susanne Kammler, Mette Kristensen, Morten O A Sommer, Harris H Wang

{"title":"Bacteria Engineered to Produce Serotonin Modulate Host Intestinal Physiology.","authors":"Chrystal F Mavros, Mareike Bongers, Frederik B F Neergaard, Frank Cusimano, Yiwei Sun, Andrew Kaufman, Miles Richardson, Susanne Kammler, Mette Kristensen, Morten O A Sommer, Harris H Wang","doi":"10.1021/acssynbio.4c00453","DOIUrl":null,"url":null,"abstract":"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 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.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Synthetic Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acssynbio.4c00453","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

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 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.

查看原文本刊更多论文

可产生羟色胺的细菌可调节宿主肠道生理机能

胃肠道中的细菌在肠道蠕动、平衡和功能障碍方面发挥着至关重要的作用。由于肠道内细菌产生或代谢的代谢物种类繁多，因此揭示微生物影响宿主的机制面临着许多挑战。在这里，我们描述了对肠道共生细菌--大肠埃希氏菌 Nissle 1917 进行工程改造，使其能生物合成人类代谢物血清素，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，我们的工程细菌会进入大肠，在那里产生血清素。用产生羟色胺的细菌处理小鼠后，肠道在转录和生理水平上发生了生物变化。这项研究建立了一个新的框架，利用工程细菌来调节腔内血清素水平，并提出了改良微生物疗法的潜在临床应用，以解决人类的肠道疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.