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Turicibacter strains differentially modify bile acids and host lipids

View ORCID ProfileJonathan B. Lynch, Erika L. Gonzalez, Kayli Choy, Kym F. Faull, Talia Jewell, Abelardo Arellano, Jennifer Liang, Kristie B. Yu, Jorge Paramo, Elaine Y. Hsiao
doi: https://doi.org/10.1101/2022.06.27.497673
Jonathan B. Lynch
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: jlynch48@jhmi.edu
Erika L. Gonzalez
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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Kayli Choy
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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Kym F. Faull
2Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA
3Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA
4Pasarow Mass Spectrometry Laboratory, University of California Los Angeles, Los Angeles, CA 90095, USA
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Talia Jewell
5Isolation Bio, San Carlos, CA 94070, USA
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Abelardo Arellano
5Isolation Bio, San Carlos, CA 94070, USA
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Jennifer Liang
5Isolation Bio, San Carlos, CA 94070, USA
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Kristie B. Yu
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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Jorge Paramo
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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Elaine Y. Hsiao
1Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA
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ABSTRACT

Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and are associated with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. We genomically and phenotypically characterized a diverse set of mouse-and human-derived Turicibacter strains, and found they group into three clades that differ in their transformations of bile acids. We identified Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Colonization with individual Turicibacter strains led to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium expressing bile-modifying genes from these strains decreased serum cholesterol and triglycerides, as well as adipose tissue mass. This work identifies genes that enable diverse Turicibacter strains to differentially modify host bile acids and lipid metabolism, and positions multiple Turicibacter strains as candidates for altering host fat biology.

Competing Interest Statement

Findings regarding the host effects of Turicibacter reported in the manuscript are the subject of provisional patent application 63/288980, owned by UCLA.

Footnotes

  • Performed statistical comparisons of metabolites to nonparametric test and correction for multiple comparisons. Added data about effects of Turicibacter and engineered Bacteroides on cecal bile profiles. Assessed transcription of liver genes in response to bacterial colonization.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 05, 2023.
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Turicibacter strains differentially modify bile acids and host lipids
Jonathan B. Lynch, Erika L. Gonzalez, Kayli Choy, Kym F. Faull, Talia Jewell, Abelardo Arellano, Jennifer Liang, Kristie B. Yu, Jorge Paramo, Elaine Y. Hsiao
bioRxiv 2022.06.27.497673; doi: https://doi.org/10.1101/2022.06.27.497673
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Turicibacter strains differentially modify bile acids and host lipids
Jonathan B. Lynch, Erika L. Gonzalez, Kayli Choy, Kym F. Faull, Talia Jewell, Abelardo Arellano, Jennifer Liang, Kristie B. Yu, Jorge Paramo, Elaine Y. Hsiao
bioRxiv 2022.06.27.497673; doi: https://doi.org/10.1101/2022.06.27.497673

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