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Title: Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

Journal Article · · Microbiology Spectrum
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [4]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [1]
  1. Univ. of Kiel (Germany)
  2. University of California, Berkeley, CA (United States)
  3. Univ. of Kiel (Germany); Max Planck Institute for Evolutionary Biology, Schleswig-Holstein (Germany)
  4. Baylor College of Medicine, Houston, TX (United States)

While numerous health-beneficial interactions between host and microbiota have been identified, there is still a lack of targeted approaches for modulating these interactions. Thus, we here identify precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In the first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we use metabolic modeling to identify precision prebiotics for a two-member Caenorhabditis elegans microbiome community comprising the immune-protective target species Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. We experimentally confirm four of the predicted precision prebiotics, L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid, to specifically increase the abundance of MYb11. L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

Research Organization:
USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); National Aeronautics and Space Administration (NASA)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2471103
Journal Information:
Microbiology Spectrum, Journal Name: Microbiology Spectrum Journal Issue: 2 Vol. 12; ISSN 2165-0497
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

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