Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

The gut microbiome provides resistance to infection. However, the mechanisms for this are poorly understood. Colonization with the intestinal bacterium Clostridium scindens provided protection from the parasite Entamoeba histolytica via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte-progenitors (GMPs) and provided neutrophil-mediated protection against subsequent challenge with E. histolytica . Adoptive transfer of bone-marrow from C. scindens colonized-mice into naïve-mice protected against ameba infection and increased intestinal neutrophils. Because of the known ability of C. scindens to metabolize the bile salt cholate, we measured deoxycholate and discovered that it was increased in the sera of C. scindens colonized mice, as well as in children protected from amebiasis. Administration of deoxycholate alone (in the absence of C. scindens ) increased the epigenetic mediator JMJD3 and GMPs and provided protection from amebiasis. In conclusion the microbiota was shown to communicate to the bone marrow via microbially-metabolized bile salts to train innate immune memory to provide antigen-nonspecific protection from subsequent infection. This represents a novel mechanism by which the microbiome protects from disease. One Sentence Summary Introduction of the human commensal bacteria Clostridium scindens into the intestinal microbiota epigenetically alters bone marrow and protects from future parasite infection.

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