(536a) Prebiotic Control of Microbial Communities with Human Milk Oligosaccharides

The synbiotic relationship between human milk oligosaccharides (HMOs) and probiotic Bifidobacteria exemplifies prebiotic control of microbial community dynamics. Inspired by this example, we have engineered the well-known probiotic, E. coli Nissle 1917, to metabolize HMOs and used this metabolism to control population dynamics and protein expression in mixed cultures of E. coli. We accomplish this using a unique whole-cell biosensor which provides linkage-specific, quantitative detection of various HMOs (Enam and Mansell, Cell Chemical Biology, 2018). Addition of these complex substrates to synthetic microbial consortia orthogonally controls growth rate or protein expression of particular strains. In addition, we performed further metabolic engineering on our probiotic, enabling production of short-chain fatty acids from HMOs as sole carbon sources, recapitulating an important function of the infant gut microbiota. Finally, we demonstrate the use of HMOs to control engineered populations in vivo in mice. This work lays the groundwork for the application of directed evolution to biosynthesis of complex carbohydrates as well as the prebiotic manipulation of population dynamics and metabolomes in natural and engineered microbial communities.