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Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis
- Source :
- EBioMedicine
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn’s disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which 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 act 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 the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.
- Subjects :
- Adult
Male
0301 basic medicine
Research paper
Faecalibacterium prausnitzii
Endogeny
Butyrate
Disease
Gut flora
Inflammatory bowel disease
General Biochemistry, Genetics and Molecular Biology
Pathogenesis
Mice
03 medical and health sciences
0302 clinical medicine
Polysaccharides
medicine
Animals
Homeostasis
Humans
Intestinal Mucosa
Symbiosis
Immunity, Mucosal
biology
Microbiota
Mucin
Mucins
General Medicine
Middle Aged
Inflammatory Bowel Diseases
biology.organism_classification
medicine.disease
Ulcerative colitis
Gastrointestinal Microbiome
Butyrates
030104 developmental biology
Case-Control Studies
030220 oncology & carcinogenesis
Immunology
Metagenome
Female
Metagenomics
Dysbiosis
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....6bf6442098f83d33f2fd53fb3875c383
- Full Text :
- https://doi.org/10.1101/655597