Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity
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Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity. / Raju, Sajan C.; Molinaro, Antonio; Awoyemi, Ayodeji; Jørgensen, Silje F.; Braadland, Peder R.; Nendl, Andraz; Seljeflot, Ingebjørg; Ueland, Per M.; McCann, Adrian; Aukrust, Pål; Vestad, Beate; Mayerhofer, Cristiane; Broch, Kaspar; Gullestad, Lars; Lappegård, Knut T.; Halvorsen, Bente; Kristiansen, Karsten; Hov, Johannes R.; Trøseid, Marius.
In: Genome Medicine, Vol. 16, No. 1, 27, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity
AU - Raju, Sajan C.
AU - Molinaro, Antonio
AU - Awoyemi, Ayodeji
AU - Jørgensen, Silje F.
AU - Braadland, Peder R.
AU - Nendl, Andraz
AU - Seljeflot, Ingebjørg
AU - Ueland, Per M.
AU - McCann, Adrian
AU - Aukrust, Pål
AU - Vestad, Beate
AU - Mayerhofer, Cristiane
AU - Broch, Kaspar
AU - Gullestad, Lars
AU - Lappegård, Knut T.
AU - Halvorsen, Bente
AU - Kristiansen, Karsten
AU - Hov, Johannes R.
AU - Trøseid, Marius
N1 - Publisher Copyright: © 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - 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: 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: 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: 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: NCT02637167, registered December 22, 2015.
AB - 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: 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: 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: 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: NCT02637167, registered December 22, 2015.
KW - Gut microbiota
KW - Heart failure
KW - Imidazole propionate
KW - Inflammation
U2 - 10.1186/s13073-024-01296-6
DO - 10.1186/s13073-024-01296-6
M3 - Journal article
C2 - 38331891
AN - SCOPUS:85184794415
VL - 16
JO - Genome Medicine
JF - Genome Medicine
SN - 1756-994X
IS - 1
M1 - 27
ER -
ID: 382994526