(182ap) Engineering Probiotics and Microbiota for Real-World Applications

The past decades have witnessed tremendous advances in engineering and developing individual microorganisms for real-world applications. However, engineering microbial communities is a very recent, challenging, but exciting development, opening a new avenue for diverse practical applications, including curing diseases, solving food inequality and shortage, facilitating sustainable bioproduction, reducing pollution, and addressing the climate crisis [1-2]. In this presentation, we will discuss the challenges and opportunities of probiotic engineering in the context of the gut or soil microbiota and based on our research. Specifically, we will briefly summarize our state-of-the-art technologies that enable the engineering of probiotics and gut microbiota, including the development of biosensors [3-5], microbiome engineering tools [6], and biocontainment approaches [7-8]. We will also explain the relatively new concept of the gut microbiota–brain axis and the unexplored issue of antibiotic resistance spread via horizontal gene transfer of antibiotic resistance genes originated from research labs. This timely work will be a resource for researchers now and in the future to integrate the core principles of probiotic and microbiota engineering.

1. TS Moon. SynMADE: Synthetic Microbiota Across Diverse Ecosystems. Trends in Biotechnology. 40, 1405-1414 (2022).
2. TS Moon. Probiotic and microbiota engineering for practical applications. Current Opinion in Food Science. 56, 101130 (2024).
3. C Xi, J Diao and TS Moon. Advances in ligand-specific biosensing for structurally similar molecules. Cell Systems. 14, 1024-1043 (2023).
4. AG Rottinghaus, C Xi, MB Amrofell, H Yi and TS Moon. Engineering ligand-specific biosensors for aromatic amino acids and neurochemicals. Cell Systems. 13, 204-214.e4 (2022)
5. C Xi, Y Ma, MB Amrofell and TS Moon. Manipulating the molecular specificity of transcriptional biosensors for tryptophan metabolites and analogs. Cell Reports Physical Science. 5, 102211 (2024)
6. AG Rottinghaus, S. Vo and TS Moon. Computational design of CRISPR guide RNAs to enable strain-specific control of microbial consortia. PNAS. 120, e2213154120 (2023).
7. AG Rottinghaus, A Ferreiro, SRS Fishbein, G Dantas and TS Moon. Genetically stable CRISPR-based kill switches for engineered microbes. Nature Communications. 13, 672 (2022)
8. Y Ma, A Manna and TS Moon. Advances in engineering genetic circuits for microbial biocontainment. Current Opinion in Systems Biology. 36, 100483 (2023).