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Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations

Authors :
Martina E. Spehlmann
Ashraf Y. Rangrez
Dhiraj P. Dhotre
Nesrin Schmiedel
Nikita Chavan
Corinna Bang
Oliver J. Müller
Yogesh S. Shouche
Andre Franke
Derk Frank
Norbert Frey
Source :
Biomedicines, Vol 10, Iss 4, p 809 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Growing evidence suggests an altered gut microbiome in patients with heart failure (HF). However, the exact interrelationship between microbiota, HF, and its consequences on the metabolome are still unknown. We thus aimed here to decipher the association between the severity and progression of HF and the gut microbiome composition and circulating metabolites. Using a mouse model of transverse aortic constriction (TAC), gut bacterial diversity was found to be significantly lower in mice as early as day 7 post-TAC compared to Sham controls (p = 0.03), with a gradual progressive decrease in alpha-diversity on days 7, 14, and 42 (p = 0.014, p = 0.0016, p = 0.0021) compared to day 0, which coincided with compensated hypertrophy, maladaptive hypertrophy, and overtly failing hearts, respectively. Strikingly, segregated analysis based on the severity of the cardiac dysfunction (EF < 40% vs. EF 40–55%) manifested marked differences in the abundance and the grouping of several taxa. Multivariate analysis of plasma metabolites and bacterial diversity produced a strong correlation of metabolic alterations, such as reduced short-chain fatty acids and an increase in primary bile acids, with a differential abundance of distinct bacteria in HF. In conclusion, we showed that HF begets HF, likely via a vicious cycle of an altered microbiome and metabolic products.

Details

Language :
English
ISSN :
22279059
Volume :
10
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.163bef2156074827b00924a0b606cbb8
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines10040809