The maternal microbiota influences the fetal development of the immune system, although previously the fetus was thought to develop in a sterile uterine environment. However, the colonization mechanisms and actual physiological effects are still unknown.
We study the development and immunological impact of the prenatal microbiota in cattle and other domestic animals. This is a readily accessible and especially interesting model for these studies. Microbes are especially important for nutrition in ruminants. Ruminants also generate their B lymphocytes in the intestine, rather than in the bone marrow. The fetal development in large domestic animals proceeds in a similar timescale as in humans, allowing the maturation of intestinal microbiota and associated immune responses. We have recently shown that in cattle, somatic hypermutation of immunoglobulins with antigen-driven signatures starts already in the bovine fetus, and our preliminary observations now indicate that microbes exist also in the fetal bovine intestine.
In this project, we characterize the fetal intestinal microbiota quantitatively and qualitatively by modern genomic sequence-driven and traditional culture-based methods, and analyze the fetal immune responses and host-microbe interactions. We will also compare the fetal microbial colonization across mammalian species with different placental structure and permeability.
The project provides new knowledge on prenatal host-microbe interactions, and how they shape the early development of the immune system. The fetal microbiota may prime the immune system for effective protection, and could induce tolerance for commensal microbes. The ability to distinguish between intestinal commensals and dangerous pathogens is one of the most critical aspects of a functional immune system, yet still poorly understood. Failure to tolerate commensals results in pathological immune responses such as inflammatory bowel diseases.
The research also has major implications in modern farm animal husbandry. The substantial early mortality in intestinal infections and the risks associated with the globally massive antibiotic use call for new prevention strategies. Rational design of such measures requires thorough understanding of early host-microbe interactions and of the fetal effects of manipulations of the maternal microbiota.
Our recent article on the early bovine intestinal microbiota:
Alipour MJ, Jalanka J, Pessa-Morikawa T, Kokkonen T, Satokari R, Hynönen U, Iivanainen A, Niku M (2018) The composition of the perinatal intestinal microbiota in cattle. Sci Rep.8(1):10437. doi: 10.1038/s41598-018-28733-y.
Open Access: https://www.nature.com/articles/s41598-018-28733-y
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