Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.

Antonio Molinaro, Andraz Nendl, Peder R Braadland, Silje F Jørgensen, Sajan C Raju, Kaspar Broch, Lars Gullestad, Per M Ueland, Johannes R Hov, Karsten Kristiansen, Cristiane Mayerhofer, Ingebjørg Seljeflot, Pål Aukrust, Bente Halvorsen, Adrian McCann, Marius Trøseid, Ayodeji Awoyemi, Knut T Lappegård, Beate Vestad

Journal: Genome medicine 2024;16(1):27

PMID: 38331891

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Abstract

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.

Address: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.; Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.; , Bevital, Bergen, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Division of Internal Medicine, Nordlandssykehuset, 8005, Bodø, Norway.; Institute of Clinical Medicine, University of Tromsø, 9037, Tromsø, Norway.; BGI-Shenzhen, Shenzhen, 518083, China.; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. [email protected].; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. [email protected].; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. [email protected].

DOI: 10.1186/s13073-024-01296-6

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MeSH Terms: Humans, Dysbiosis, Heart Failure, Imidazoles, Microbiota, Patient Acuity