Inflammation and
infection are key promoters of
colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in
leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of
arthritis,
asthma and
atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous
tumor (ApcMin/+) model displayed an increase in the rate of intestinal
tumor development and mortality. A paradoxical increase in
inflammation in the
tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to
infection. Germ-free BLT1-/-ApcMin/+ mice are free from colon
tumors that reappeared upon
fecal transplantation. Analysis of microbiota showed defective host response in BLT1-/- ApcMin/+ mice reshapes the gut microbiota to promote colon
tumor development. The BLT1-/-MyD88-/- double deficient mice are susceptible to lethal neonatal
infections. Broad-spectrum
antibiotic treatment eliminated neonatal lethality in BLT1-/-MyD88-/- mice and the BLT1-/-MyD88-/-ApcMin+ mice are protected from colon
tumor development. These results identify a novel interplay between the
Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon
tumor development.