Multi-omics analyses of the ulcerative colitis gut microbiome link Bacteroides vulgatus proteases with disease severity.
Adult
Animals
Bacterial Proteins
/ classification
Bacteroides
/ enzymology
Cohort Studies
Colitis, Ulcerative
/ microbiology
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ genetics
Humans
Longitudinal Studies
Male
Metagenome
Metagenomics
/ methods
Mice
Middle Aged
Peptide Hydrolases
/ classification
Proteomics
/ methods
Severity of Illness Index
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
15
09
2021
accepted:
15
12
2021
pubmed:
29
1
2022
medline:
23
2
2022
entrez:
28
1
2022
Statut:
ppublish
Résumé
Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.
Identifiants
pubmed: 35087228
doi: 10.1038/s41564-021-01050-3
pii: 10.1038/s41564-021-01050-3
pmc: PMC8852248
mid: NIHMS1764988
doi:
Substances chimiques
Bacterial Proteins
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
262-276Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007202
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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