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

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 an...

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Autores principales: Spehlmann, Martina E., Rangrez, Ashraf Y., Dhotre, Dhiraj P., Schmiedel, Nesrin, Chavan, Nikita, Bang, Corinna, Müller, Oliver J., Shouche, Yogesh S., Franke, Andre, Frank, Derk, Frey, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033061/
https://www.ncbi.nlm.nih.gov/pubmed/35453559
http://dx.doi.org/10.3390/biomedicines10040809
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author Spehlmann, Martina E.
Rangrez, Ashraf Y.
Dhotre, Dhiraj P.
Schmiedel, Nesrin
Chavan, Nikita
Bang, Corinna
Müller, Oliver J.
Shouche, Yogesh S.
Franke, Andre
Frank, Derk
Frey, Norbert
author_facet Spehlmann, Martina E.
Rangrez, Ashraf Y.
Dhotre, Dhiraj P.
Schmiedel, Nesrin
Chavan, Nikita
Bang, Corinna
Müller, Oliver J.
Shouche, Yogesh S.
Franke, Andre
Frank, Derk
Frey, Norbert
author_sort Spehlmann, Martina E.
collection PubMed
description 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.
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spelling pubmed-90330612022-04-23 Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations Spehlmann, Martina E. Rangrez, Ashraf Y. Dhotre, Dhiraj P. Schmiedel, Nesrin Chavan, Nikita Bang, Corinna Müller, Oliver J. Shouche, Yogesh S. Franke, Andre Frank, Derk Frey, Norbert Biomedicines Article 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. MDPI 2022-03-30 /pmc/articles/PMC9033061/ /pubmed/35453559 http://dx.doi.org/10.3390/biomedicines10040809 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Spehlmann, Martina E.
Rangrez, Ashraf Y.
Dhotre, Dhiraj P.
Schmiedel, Nesrin
Chavan, Nikita
Bang, Corinna
Müller, Oliver J.
Shouche, Yogesh S.
Franke, Andre
Frank, Derk
Frey, Norbert
Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title_full Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title_fullStr Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title_full_unstemmed Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title_short Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations
title_sort heart failure severity closely correlates with intestinal dysbiosis and subsequent metabolomic alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033061/
https://www.ncbi.nlm.nih.gov/pubmed/35453559
http://dx.doi.org/10.3390/biomedicines10040809
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