Gut microbiome communication with bone marrow regulates susceptibility to amebiasis
Stacey L. Burgess, … , Rashidul Haque, William A. Petri Jr.
Stacey L. Burgess, … , Rashidul Haque, William A. Petri Jr.
Published May 5, 2020
Citation Information: J Clin Invest. 2020;130(8):4019-4024. https://doi.org/10.1172/JCI133605.
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Concise Communication Immunology Infectious disease

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

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.

Authors

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

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Figure 4

C.scindens colonization increases serum deoxycholic acid (DCA), and administration of DCA expanded marrow GMPs and intestinal neutrophils and protected from amoebic colitis.

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C.scindens colonization increases serum deoxycholic acid (DCA), and adm...
(A) CBA/J mice were colonized with C. scindens over 3 weeks via gavage and serum DCA was measured at 10 weeks of age in control BHI media–gavaged mice and C. scindens–gavaged mice. (B) Serum DCA was measured via ELISA in 2-year-old children in Bangladesh free of (–) or infected with (+) E. histolytica within 6 months of the blood draw. n = 40 children per condition. (C–G) Mice were administered DCA or PBS intravenously 3 times a week for 2 weeks and then challenged with E. histolytica. Serum DCA was measured at the end of week 1 (day –7) (C) and at the end of the experiment (day 6) (D). (E) E. histolytica infection, (F) change in marrow GMPs, and (G) intestinal neutrophils were measured at the end of the experiment. *P < 0.05 by Student’s t test (A–D, F, and G) or Mann-Whitney U test (E). n = 6–8 mice per group.