Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice.

Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis. This study evaluates the effect of fucose on reproductive performance in heterozygous mutant Muc2 female mice. We found that even though Muc2+/- females are physiologically indistinguishable from C57Bl/6 mice, they have a significantly reduced reproductive performance upon dietary fucose supplementation. Metagenomic analysis reveals that the otherwise healthy wild-type siblings of Muc2-/- animals have reduced numbers of some of the intestinal commensal bacterial species, compared to C57BL/6 mice. We propose that the changes in beneficial microflora affect the immune status in Muc2+/- mice, which causes implantation impairment. In accordance with this hypothesis, we find that macrophage polarization during pregnancy is impaired in Muc2+/- females upon addition of fucose. Metabolic profiling of peritoneal macrophages from Muc2+/- females reveals their predisposition towards anaerobic glycolysis in favor of oxidative phosphorylation, compared to C57BL/6-derived cells. In vitro experiments on phagocytosis activity and mitochondrial respiration suggest that fucose affects oxidative phosphorylation in a genotype-specific manner, which might interfere with implantation depending on the initial status of macrophages. This hypothesis is further confirmed in BALB/c female mice, where fucose caused pregnancy loss and opposed implantation-associated M2 macrophage polarization. Taken together, these data suggest that intestinal microflora affects host immunity and pregnancy outcome. At the same time, dietary fucose might act as a differential regulator of macrophage polarization during implantation, depending on the immune status of the host.

Modification of Fecal Bacteria Counts and Blood Immune Cells in the Offspring of BALB/c and C57BL/6 Mice Obtained through Interstrain Mouse Embryo Transfer.

The reproducibility of results obtained with rodent models depends on the genetic purity of the strain and the stability of the environment. However, another potential factor is changes in the gut microbiota due to the transmission of mother's bacteria during embryo transfer. In this study, we demonstrate the transmission of the microbiota and immune cell blood phenotype to the offspring of 2 strains, C57BL/6JNskrc and BALB/cJNskrc, from surrogate dams of different genotypes. Interstrain embryo transfer resulted in a change in the number of Enterococcus spp. organisms, as shown by quantitative PCR analysis. The number of blood leukocytes was also affected, as estimated by flow cytometry. The number of blood leukocytes, including B cells and helper T cells, and the number of Enterococcus spp. organisms in male C57BL/6JNskrc offspring bornto BALB/cJNskrc surrogate dams became similar to those of male BALB/cJNskrc mice born to BALB/cJNskrc dams. Likewise, the same parameters of male BALB/cJNskrc mice born to C57BL/6JNskrc dams became similar to those of male C57BL/6JNskrc offspring. Researchers should be aware of the possible transmission of the dam's microbiota and immune cell phenotypes to the experimental strains when planning embryo transfer experiments, because these factors could affect the experimental outcomes or the reproducibility of experimental results.