Furthermore, an isogenic HDC-deficient L. reuteri mutant that was unable to generate histamine did not suppress carcinogenesis, indicating a significant role of the cometabolite, histamine, in suppression of chronic intestinal inflammation and colorectal tumorigenesis.
The enzyme histidine decarboxylase (Hdc), which generates histamine, is highly expressed in CD11b<sup>+</sup>Gr-1<sup>+</sup> myeloid cells that play a critical role in infection, inflammation and tumorigenesis.
Lineage tracing in Hdc-CreERT2;R26-LSL-tdTomato mice revealed that in homeostasis, there is a strong bias by HDC<sup>+</sup> myeloid cells toward the CD11b<sup>+</sup>Ly6G<sup>hi</sup> granulocytic lineage, which was accelerated during azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic carcinogenesis.