Journal
EBIOMEDICINE
Volume 48, Issue -, Pages 513-525Publisher
ELSEVIER
DOI: 10.1016/j.ebiom.2019.09.008
Keywords
Microbiota; Butyrate; Mucin; Inflammatory bowel disease
Funding
- Japan Society for the Promotion of Science [16H01369, 17KT0055, 18H04680]
- Health Labour Sciences Research Grant
- AMED-Crest [16gm0000000h0101, 17gm1010004h0102, 18gm1010004h0103]
- AMED [18ek0109303h0001]
- Yakult Foundation
- Keio Gijuku Academic Development Funds
- Aashi Grass Foundation
- Canon Foundation
- Grants-in-Aid for Scientific Research [17KT0055, 16H01369, 18H04680] Funding Source: KAKEN
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Background: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth. Methods: To elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from japan. Findings: Levels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt(+)Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients. Interpretation: Mucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients. Fund: Japan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation. (C) 2019 The Authors. Published by Elsevier B.V.
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