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Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis
Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E. histolytica. Introduction of C. scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C. scindens–colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E. histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C. scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C. scindens–colonized specific pathogen–free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C. scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E. histolytica.

0021-9738
4019-4024
Burgess, Stacey L.
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Leslie, Jhansi L.
4354de47-e2d9-4701-a57b-59ebd8f723c7
Uddin, Md Jashim
cc56d808-87af-4b14-a10c-ab5e6909ba2c
Oakland, David Noah
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Gilchrist, Carol A.
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Moreau, G. Brett
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Watanabe, Koji
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Saleh, Mahmoud M.
afa55ce2-cf6e-4bb9-b6e0-ca4225024da1
Simpson, Morgan
c7992d6a-a231-4f78-80aa-054887d7460e
Thompson, Brandon A.
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Auble, David T.
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Turner, Stephen D.
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Giallourou, Natasa
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Swann, Jonathan
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Pu, Zhen
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Ma, Jennie Z.
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Haque, Rashidul
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Petri, William A.
bea028a7-81ab-42e6-b790-611d8f58133a
Burgess, Stacey L.
dcb4edc4-e83d-4baa-ac04-46be82cf727a
Leslie, Jhansi L.
4354de47-e2d9-4701-a57b-59ebd8f723c7
Uddin, Md Jashim
cc56d808-87af-4b14-a10c-ab5e6909ba2c
Oakland, David Noah
47a9740c-7dca-4729-951d-8f7c1a7f9bd9
Gilchrist, Carol A.
453377eb-6285-4ea2-9da1-5e9b1f8c8c2a
Moreau, G. Brett
c4491dd9-6640-44eb-88c5-82ec77932987
Watanabe, Koji
a28badce-cafb-4390-838a-3b6b74a11de6
Saleh, Mahmoud M.
afa55ce2-cf6e-4bb9-b6e0-ca4225024da1
Simpson, Morgan
c7992d6a-a231-4f78-80aa-054887d7460e
Thompson, Brandon A.
f79e9fec-aca4-4f92-a5d6-44a822d501f0
Auble, David T.
bdaf1da3-cc78-4881-acaf-e8c452946d3e
Turner, Stephen D.
b2e6a289-5a68-47d1-9164-23681d69f259
Giallourou, Natasa
b5891ea7-98d4-49d7-b883-2c57ca2d962a
Swann, Jonathan
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Pu, Zhen
4e5f2268-4ea8-411a-a82f-7a2a03535d62
Ma, Jennie Z.
64271b17-b687-46c5-a52d-cda1146adf13
Haque, Rashidul
9155e10d-7434-4a6e-9dde-0775526dc6b5
Petri, William A.
bea028a7-81ab-42e6-b790-611d8f58133a

Burgess, Stacey L., Leslie, Jhansi L., Uddin, Md Jashim, Oakland, David Noah, Gilchrist, Carol A., Moreau, G. Brett, Watanabe, Koji, Saleh, Mahmoud M., Simpson, Morgan, Thompson, Brandon A., Auble, David T., Turner, Stephen D., Giallourou, Natasa, Swann, Jonathan, Pu, Zhen, Ma, Jennie Z., Haque, Rashidul and Petri, William A. (2020) Gut microbiome communication with bone marrow regulates susceptibility to amebiasis. Journal of Clinical Investigation, 140 (8), 4019-4024. (doi:10.1172/JCI133605).

Record type: Article

Abstract

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E. histolytica. Introduction of C. scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C. scindens–colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E. histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C. scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C. scindens–colonized specific pathogen–free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C. scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E. histolytica.

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More information

e-pub ahead of print date: 5 May 2020
Published date: 3 August 2020
Additional Information: Funding Information: We thank Tuhinur Arju, and Mamun Kabir at icddr,b. At the University of Virginia, we thank Jeremy Gatesman, Homer Ransdell, Alice Kenney and Sanford Feldman at the Center for Comparative Medicine, Michael Solga, Claude Chew, and Joanne Lannigan at the Flow Cytometry Core facility, AhnThu Nguyen at the Biology Department Genomics Core, Katia Sol-Church and Alyson Pro-rock at the Genome Analysis and Technology Core, and Todd Fox at the Metabolomics Core; and EpiGentek for technical support. We thank Emery H. Bresnick at UW-Madison for helpful scientific discussions. This work was supported by NIH National Institute of Allergy and Infectious Diseases (NIAID) grants R01 AI-26649 and R01 AI043596 (to WAP), by T 32 5T32AI007046 from the Bill and Melinda Gates Foundation, by Robert and Elizabeth Henske, and by NIAID grants R21 AI130700 and R01 AI146257 (to SLB). Publisher Copyright: Copyright: © 2020 Burgess et al.

Identifiers

Local EPrints ID: 440762
URI: http://eprints.soton.ac.uk/id/eprint/440762
ISSN: 0021-9738
PURE UUID: c5ec8ddf-fb11-42cb-8865-8a90c9809c62
ORCID for Jonathan Swann: ORCID iD orcid.org/0000-0002-6485-4529

Catalogue record

Date deposited: 15 May 2020 16:56
Last modified: 29 Sep 2022 01:59

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Contributors

Author: Stacey L. Burgess
Author: Jhansi L. Leslie
Author: Md Jashim Uddin
Author: David Noah Oakland
Author: Carol A. Gilchrist
Author: G. Brett Moreau
Author: Koji Watanabe
Author: Mahmoud M. Saleh
Author: Morgan Simpson
Author: Brandon A. Thompson
Author: David T. Auble
Author: Stephen D. Turner
Author: Natasa Giallourou
Author: Jonathan Swann ORCID iD
Author: Zhen Pu
Author: Jennie Z. Ma
Author: Rashidul Haque
Author: William A. Petri

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