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  Mucus sialylation determines intestinal host-commensal homeostasis

Yao, Y., Kim, G., Shafer, S., Chen, Z., Kubo, S., Ji, Y., et al. (2022). Mucus sialylation determines intestinal host-commensal homeostasis. Cell, 185(7), 1172-1188.e28. doi:10.1016/j.cell.2022.02.013.

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Genre: Journal Article

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 Creators:
Yao, Y., Author
Kim, G., Author
Shafer, S., Author
Chen, Z., Author
Kubo, S., Author
Ji, Y.1, Author              
Luo, Ji., Author
Yang, W., Author
Perner, S. P., Author
Kanellopoulou, C., Author
Park, A. Y., Author
Jiang, Pi., Author
Li, J., Author
Baris, S., Author
Aydiner, E.K., Author
Ertem, De., Author
Mulder, D. J., Author
Warner, N., Author
Griffiths, A. M., Author
Topf-Olivestone, C., Author
Kori, M., AuthorWerner, L.., AuthorOuahed, J., AuthorField, M., AuthorLiu, C., AuthorSchwarz, B., AuthorBosio, C. M., AuthorGanesan, S., AuthorSong, J., AuthorUrlaub, H.1, Author              Oellerich, T., AuthorMalaker, S. A., AuthorZheng, L., AuthorBertozzi, C. R., AuthorZhang, Y., AuthorMatthews, H., AuthorMontgomery, W., AuthorShih, H.-Y., AuthorJiang, J., AuthorJones, Ma., AuthorBaras, A., AuthorShuldiner, A., AuthorGonzaga-Jauregui, C., AuthorSnapper, S. B., AuthorMuise, A. M., AuthorShouval, D. S., AuthorOzen, A., AuthorPan, K.-T., AuthorWu, C., AuthorLenardo, M. J., Author more..
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              

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Free keywords: glycobiology; sialylation; human genetic disease; inflammatory bowel; disease; ST6GalNAc1; mucus barrier; intestinal homeostasis; dysbiosis; short-chain fatty acids; intestinal stem cells
 Abstract: Intestinal mucus forms the first line of defense against bacterial invasion while providing nutrition to support microbial symbiosis. How the host controls mucus barrier integrity and commensalism is unclear. We show that terminal sialylation of glycans on intestinal mucus by ST6GALNAC1 (ST6), the dominant sialyltransferase specifically expressed in goblet cells and induced by microbial pathogen-associated molecular patterns, is essential for mucus integrity and protecting against excessive bacterial proteolytic degradation. Glycoproteomic profiling and biochemical analysis of ST6 mutations identified in patients show that decreased sialylation causes defective mucus proteins and congenital inflammatory bowel disease (IBD). Mice harboring a patient ST6 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation. Based on our understanding of the ST6 regulatory network, we show that treatment with sialylated mucin or a Foxo3 inhibitor can ameliorate IBD.

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Language(s): eng - English
 Dates: 2022-03-172022-03-31
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cell.2022.02.013
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 185 (7) Sequence Number: - Start / End Page: 1172 - 1188.e28 Identifier: ISSN: 00928674