Gut commensals expand vitamin A metabolic capacity of the mammalian host

Maryam Bonakdar; Lindsay C. Czuba; Geongoo Han; Guo Zhong; Hien Luong; Nina Isoherrannen; Shipra Vaishnava

doi:10.1016/j.chom.2022.06.011

Gut commensals expand vitamin A metabolic capacity of the mammalian host

Maryam Bonakdar, Lindsay C. Czuba, Geongoo Han, Guo Zhong, Hien Luong, Nina Isoherrannen, Shipra Vaishnava

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.

Original language	English
Pages (from-to)	1084-1092.e5
Journal	Cell Host and Microbe
Volume	30
Issue number	8
DOIs	https://doi.org/10.1016/j.chom.2022.06.011
State	Published - Aug 10 2022

Bibliographical note

Funding Information:
This work was supported by the NIH ( R01DK113265 ) to S.V. and R01 GM111772 to N.I. N.I. is supported by the School of Pharmacy’s Milo GIbaldi Endowed Chair . M.B. was a trainee supported under the Brown University Predoctoral Training Program in Biological Data Science ( NIH T32 GM128596 ).

Funding Information:
This work was supported by the NIH (R01DK113265) to S.V. and R01 GM111772 to N.I. N.I. is supported by the School of Pharmacy's Milo GIbaldi Endowed Chair. M.B. was a trainee supported under the Brown University Predoctoral Training Program in Biological Data Science (NIH T32 GM128596). Conceptualization, S.V. and M.B.; methodology, S.V. M.B. L.C.C. G.H. G.Z. H.L. and N.I.; investigation, S.V. M.B. L.C.C. and N.I.; writing – original draft, S.V. and M.B.; writing – review & editing, S.V. M.B. L.C.C. and N.I.; funding acquisition, S.V. and N.I.; resources, S.V. and N.I.; supervision, S.V. and N.I. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

13-cis-retinoic acid
LC-MS/MS
all-trans-retinoic acid
germ-free mice
microbiome
retinol
vitamin A metabolism

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2022.06.011

Cite this

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title = "Gut commensals expand vitamin A metabolic capacity of the mammalian host",

abstract = "Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.",

keywords = "13-cis-retinoic acid, LC-MS/MS, all-trans-retinoic acid, germ-free mice, microbiome, retinol, vitamin A metabolism",

author = "Maryam Bonakdar and Czuba, {Lindsay C.} and Geongoo Han and Guo Zhong and Hien Luong and Nina Isoherrannen and Shipra Vaishnava",

note = "Funding Information: This work was supported by the NIH ( R01DK113265 ) to S.V. and R01 GM111772 to N.I. N.I. is supported by the School of Pharmacy{\textquoteright}s Milo GIbaldi Endowed Chair . M.B. was a trainee supported under the Brown University Predoctoral Training Program in Biological Data Science ( NIH T32 GM128596 ). Funding Information: This work was supported by the NIH (R01DK113265) to S.V. and R01 GM111772 to N.I. N.I. is supported by the School of Pharmacy's Milo GIbaldi Endowed Chair. M.B. was a trainee supported under the Brown University Predoctoral Training Program in Biological Data Science (NIH T32 GM128596). Conceptualization, S.V. and M.B.; methodology, S.V. M.B. L.C.C. G.H. G.Z. H.L. and N.I.; investigation, S.V. M.B. L.C.C. and N.I.; writing – original draft, S.V. and M.B.; writing – review & editing, S.V. M.B. L.C.C. and N.I.; funding acquisition, S.V. and N.I.; resources, S.V. and N.I.; supervision, S.V. and N.I. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

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AU - Isoherrannen, Nina

AU - Vaishnava, Shipra

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N2 - Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.

AB - Conversion of dietary vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced a high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis-retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anerobic bacteria significantly reduced retinol, atRA, and 13cisRA, whereas introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy.

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Gut commensals expand vitamin A metabolic capacity of the mammalian host

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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