益生菌
大肠杆菌
微生物学
生物
肠道菌群
长双歧杆菌
体内
代谢工程
乳酸
双歧杆菌
细菌
生物化学
乳酸菌
发酵
生物技术
酶
遗传学
基因
作者
Chrysoula Dimopoulou,Mareike Bongers,Mikael Pedersen,Martin Iain Bahl,Morten Otto Alexander Sommer,Martin Frederik Laursen,Tine Rask Licht
出处
期刊:Fems Microbiology Letters
[Oxford University Press]
日期:2023-01-01
卷期号:370
被引量:1
标识
DOI:10.1093/femsle/fnad027
摘要
Abstract The expanding knowledge of the health impacts of the metabolic activities of the gut microbiota reinforces the current interest in engineered probiotics. Tryptophan metabolites, in particular indole lactic acid (ILA), are attractive candidates as potential therapeutic agents. ILA is a promising compound with multiple beneficial effects, including amelioration colitis in rodent models of necrotizing enterocolitis, as well as improved infant immune system maturation. In this work, we engineered and characterized in vitro and in vivo an Escherichia coli Nissle 1917 strain that produces ILA. The 2-step metabolic pathway comprises aminotransferases native of E. coli and a dehydrogenase introduced from Bifidobacterium longum subspecies infantis. Our results show a robust engineered probiotic that produces 73.4 ± 47.2 nmol and 149 ± 123.6 nmol of ILA per gram of fecal and cecal matter, respectively, three days after colonization in a mouse model. In addition, hereby is reported an engineered-probiotic-related increase of ILA in the systemic circulation of the treated mice. This strain serves as proof of concept for the transfer of capacity to produce ILA in vivo and as ILA emerges as a potent microbial metabolite against gastrointestinal inflammation, further development of this strain offers efficient options for ILA-focused therapeutic interventions in situ.
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