Differential contributions of the gut microbiota and metabolome to pathomechanisms in ulcerative colitis: an in vitro analysis

Autor: Jonas Poppe, Leen Boesmans, Sara Vieira-Silva, Lise Deroover, Raul Tito, Doris Vandeputte, Greet Vandermeulen, Vicky De Preter, Jeroen Raes, Severine Vermeire, Gwen Falony, Kristin Verbeke
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Gut Microbes, Vol 16, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2024.2424913
Popis: The gut microbiota has been implicated in onset and progression of ulcerative colitis (UC). Here, we assess potential causal involvement of the microbiota and -associated fecal water (FW) metabolome in altering key functional parameters of the colonic epithelium. Fecal samples were collected from N = 51 healthy controls (HC), N = 36 patients with active UC (UC-A), and N = 41 subjects in remission N = 41 (UC-R). Using in vitro incubation experiments, the FW metabolome’s impact on butyrate oxidation rates/gene expression and cell death (cytotoxicity) of HT-29 cells, cytokine production by PBMC, and barrier integrity of Caco2 monolayers was evaluated. The FW metabolome from patients and individuals hosting the Bacteroides 2 (Bact2) enterotype (69% of UC-A, 31% of UC-R, 3% of HC), characterized by lower levels of median- and short-chain fatty acids and furan compounds, left butyrate oxidation rates unaltered but affected associated gene expression profiles. UC patients/Bact2-carriers’ FW lowered PBMC IL-8 production and increased IL-1β production. Patients’ FW increased cytotoxicity, associated with sulfide compound levels. Bact2 carriers’ FW, displaying higher levels of bile acids, lowered barrier function upon incubation of monolayers. The FW metabolome of patients and individuals hosting a dysbiotic microbiota could contribute to the disruption of functional processes of the colonic epithelium as observed in UC.
Databáze: Directory of Open Access Journals
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