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Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages
Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon, South Korea.
Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Daejeon, South Korea.
Inst for Basic Sci Korea, Ctr Vasc Res, Daejeon, South Korea.
Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon, South Korea.
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2019 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 20, no 4, article id e46927Article in journal (Refereed) Published
Abstract [en]

A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 20, no 4, article id e46927
Keywords [en]
intestinal lymphatic vasculature, lacteal, macrophage, microbiota, VEGF-C
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-382513DOI: 10.15252/embr.201846927ISI: 000463235300015PubMedID: 30783017OAI: oai:DiVA.org:uu-382513DiVA, id: diva2:1308039
Available from: 2019-04-30 Created: 2019-04-30 Last updated: 2019-04-30Bibliographically approved

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Mäkinen, Taija

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