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Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice

Scientific-Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia
Siberian Federal Scientific Centre of Agro-BioTechnologies of the Russian Academy of Sciences, Krasnoobsk, 630501 Novosibirsk Region, Russia
Faculty of Veterinary Medicine, Novosibirsk State Agrarian University, 630039 Novosibirsk, Russia
Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia
Institute of Molecular and Cellular Biology, The Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
Author to whom correspondence should be addressed.
Nutrients 2021, 13(3), 855;
Received: 22 February 2021 / Accepted: 2 March 2021 / Published: 5 March 2021
(This article belongs to the Section Nutrition and Public Health)
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. View Full-Text
Keywords: Mucin 2; embryo implantation; fucose; macrophages; immune response; pregnancy Mucin 2; embryo implantation; fucose; macrophages; immune response; pregnancy
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MDPI and ACS Style

Litvinova, E.A.; Bets, V.D.; Feofanova, N.A.; Gvozdeva, O.V.; Achasova, K.M.; Alperina, E.L.; Kozhevnikova, E.N. Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice. Nutrients 2021, 13, 855.

AMA Style

Litvinova EA, Bets VD, Feofanova NA, Gvozdeva OV, Achasova KM, Alperina EL, Kozhevnikova EN. Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice. Nutrients. 2021; 13(3):855.

Chicago/Turabian Style

Litvinova, Ekaterina A.; Bets, Victoria D.; Feofanova, Natalya A.; Gvozdeva, Olga V.; Achasova, Kseniya M.; Alperina, Elizaveta L.; Kozhevnikova, Elena N. 2021. "Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice" Nutrients 13, no. 3: 855.

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