"Lipocalin 2 protects from colonic inflammation and tumorigenesis through its microbiota modulating properties"

"The siderophore-binding peptide Lipocalin-2 (Lcn2) is involved in host defense against pathogens. Lcn2 function in intestinal mucosal immunity remains largely unknown. Here, we demonstrate that Lcn2 protects from early-onset colitis and spontaneous emergence of right-sided colonic tumors in Il10–/– mice. Bone marrow chimeric experiments indicate that both hematopoietic and non-hematopoietic Lcn2 is protective. Exacerbating inflammation in double-deficient Lcn2–/– / Il10–/– mice is driven by IL-6 which also controls tumorigenesis. Lcn2–/– / Il10–/– mice exhibit profound alterations in gut microbial composition which contributes to inflammation and tumorigenesis as demonstrated by the transmissibility of the phenotype by microbiota transfer and by protection conferred by antibiotics. Facultative pathogenic Alistipes spp. that bloom in Lcn2–/– / Il10–/– mice induce colitis and right-sided tumors when transferred into Il10–/– mice. Our results demonstrate that Lcn2 protects against intestinal inflammation and tumorigenesis through modulation of the microbiota. "