Metabolic engineering of human gut microbiome: Recent developments and future perspectives

• Published in: Metabolic engineering Vol. 79; pp. 1 - 13
• Main Authors: Li, Peishun, Roos, Stefan, Luo, Hao, Ji, Boyang, Nielsen, Jens
• Format: Journal Article
• Language: English
• Published: Belgium Elsevier Inc 01.09.2023
• Subjects: Engineered microbes; Gut microbiome; Metabolic modeling; Microbial consortia; Probiotics; Engineered microbes; Probiotics; Metabolic modeling; Gut microbiome; Microbial consortia
• ISSN: 1096-7176; 1096-7184; 1096-7184
• DOI: 10.1016/j.ymben.2023.06.006

Many studies have demonstrated that the gut microbiota is associated with human health and disease. Manipulation of the gut microbiota, e.g. supplementation of probiotics, has been suggested to be feasible, but subject to limited therapeutic efficacy. To develop efficient microbiota-targeted diagnostic and therapeutic strategies, metabolic engineering has been applied to construct genetically modified probiotics and synthetic microbial consortia. This review mainly discusses commonly adopted strategies for metabolic engineering in the human gut microbiome, including the use of in silico, in vitro, or in vivo approaches for iterative design and construction of engineered probiotics or microbial consortia. Especially, we highlight how genome-scale metabolic models can be applied to advance our understanding of the gut microbiota. Also, we review the recent applications of metabolic engineering in gut microbiome studies as well as discuss important challenges and opportunities. •An adapted iterative cycle of Learn-Design-Build-Test (LDBT) for engineering the human gut microbiome was proposed.•How genome-scale metabolic models and community models can be applied to understand the gut microbiota was elaborated.•Recent progress of metabolic engineering in gut microbiome field was summarized.•Critical challenges and opportunities for metabolic engineering of gut microbiota were discussed.