Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.
Gut microbiota
Heart failure
Imidazole propionate
Inflammation
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
08 Feb 2024
08 Feb 2024
Historique:
received:
18
10
2023
accepted:
23
01
2024
medline:
9
2
2024
pubmed:
9
2
2024
entrez:
8
2
2024
Statut:
epublish
Résumé
Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking. We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines. Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation. Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis. NCT02637167, registered December 22, 2015.
Sections du résumé
BACKGROUND
BACKGROUND
Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking.
METHODS
METHODS
We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines.
RESULTS
RESULTS
Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation.
CONCLUSIONS
CONCLUSIONS
Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis.
TRIAL REGISTRATION
BACKGROUND
NCT02637167, registered December 22, 2015.
Identifiants
pubmed: 38331891
doi: 10.1186/s13073-024-01296-6
pii: 10.1186/s13073-024-01296-6
doi:
Banques de données
ClinicalTrials.gov
['NCT02637167']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
27Subventions
Organisme : Norges Forskningsråd
ID : 287242
Informations de copyright
© 2024. The Author(s).
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