Abstract
Endogenous intestinal microbiota have wide-ranging and largely uncharacterized effects on host physiology. Here, we used reverse-phase liquid chromatography-coupled tandem mass spectrometry to define the mouse intestinal proteome in the stomach, jejunum, ileum, cecum and proximal colon under three colonization states: germ-free (GF), monocolonized with Bacteroides thetaiotaomicron and conventionally raised (CR). Our analysis revealed distinct proteomic abundance profiles along the gastrointestinal (GI) tract. Unsupervised clustering showed that host protein abundance primarily depended on GI location rather than colonization state and specific proteins and functions that defined these locations were identified by random forest classifications. K-means clustering of protein abundance across locations revealed substantial differences in host protein production between CR mice relative to GF and monocolonized mice. Finally, comparison with fecal proteomic data sets suggested that the identities of stool proteins are not biased to any region of the GI tract, but are substantially impacted by the microbiota in the distal colon.
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Acknowledgements
We would like to thank members of the Elias and Sonnenburg lab members, Carlos Gonzales and Katherine Ng for artistic support; and teaching assistants Alexandre Colavin, Miriam Gutschow and Sam Smits for helpful feedback. This work was supported by a Curriculum Development Award from The MathWorks, Inc. (to KCH and JLS), a grant from the National Institutes of Health (R01-DK085025) (to JLS), the Stanford Systems Biology Center funded by National Institutes of Health grant P50 GM107615 (to KCH) and grant DGE-114747 from the National Science Foundation (to JSL).
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Lichtman, J., Alsentzer, E., Jaffe, M. et al. The effect of microbial colonization on the host proteome varies by gastrointestinal location. ISME J 10, 1170–1181 (2016). https://doi.org/10.1038/ismej.2015.187
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DOI: https://doi.org/10.1038/ismej.2015.187
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