Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis

Aims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations...

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Autores principales: Tomohiro Hayashi, Tomoya Yamashita, Tomoya Takahashi, Tokiko Tabata, Hikaru Watanabe, Yasuhiro Gotoh, Masakazu Shinohara, Kenjiro Kami, Hidekazu Tanaka, Kensuke Matsumoto, Tetsuya Hayashi, Takuji Yamada, Ken-ichi Hirata
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/e4bce4d3ccba4999961682680d432511
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spelling oai:doaj.org-article:e4bce4d3ccba4999961682680d4325112021-12-01T13:35:46ZUncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis2297-055X10.3389/fcvm.2021.789325https://doaj.org/article/e4bce4d3ccba4999961682680d4325112021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.789325/fullhttps://doaj.org/toc/2297-055XAims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.Methods and Results: We performed whole-genome shotgun sequencing of fecal samples and mass spectrometry-based profiling of AAs in patients with compensated HF. Plasma levels of total essential AAs (EAAs) and histidine were significantly lower in patients with HF than in control subjects. HF patients also displayed increased and decreased abundance of gut microbial genes involved in the degradation and biosynthesis, respectively, of EAAs, including branched-chain AAs (BCAAs) and histidine. Importantly, a significant positive correlation was observed between the abundance of microbial genes involved in BCAA biosynthesis and plasma BCAA levels in patients with HF, but not in controls. Moreover, network analysis revealed that the depletion of Eubacterium and Prevotella, which harbor genes for BCAA and histidine biosynthesis, contributed to decreased abundance of microbial genes involved in the biosynthesis of those EAAs in patients with HF.Conclusions: The present study demonstrated the relationship between gut microbiota and AA metabolic disturbances in patients with HF.Tomohiro HayashiTomohiro HayashiTomoya YamashitaTomoya TakahashiTokiko TabataHikaru WatanabeYasuhiro GotohMasakazu ShinoharaMasakazu ShinoharaKenjiro KamiHidekazu TanakaKensuke MatsumotoTetsuya HayashiTakuji YamadaKen-ichi HirataFrontiers Media S.A.articleheart failuregut microbiotaamino acid (AA)metabolismmetagenomic analysisDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic heart failure
gut microbiota
amino acid (AA)
metabolism
metagenomic analysis
Diseases of the circulatory (Cardiovascular) system
RC666-701
spellingShingle heart failure
gut microbiota
amino acid (AA)
metabolism
metagenomic analysis
Diseases of the circulatory (Cardiovascular) system
RC666-701
Tomohiro Hayashi
Tomohiro Hayashi
Tomoya Yamashita
Tomoya Takahashi
Tokiko Tabata
Hikaru Watanabe
Yasuhiro Gotoh
Masakazu Shinohara
Masakazu Shinohara
Kenjiro Kami
Hidekazu Tanaka
Kensuke Matsumoto
Tetsuya Hayashi
Takuji Yamada
Ken-ichi Hirata
Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
description Aims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.Methods and Results: We performed whole-genome shotgun sequencing of fecal samples and mass spectrometry-based profiling of AAs in patients with compensated HF. Plasma levels of total essential AAs (EAAs) and histidine were significantly lower in patients with HF than in control subjects. HF patients also displayed increased and decreased abundance of gut microbial genes involved in the degradation and biosynthesis, respectively, of EAAs, including branched-chain AAs (BCAAs) and histidine. Importantly, a significant positive correlation was observed between the abundance of microbial genes involved in BCAA biosynthesis and plasma BCAA levels in patients with HF, but not in controls. Moreover, network analysis revealed that the depletion of Eubacterium and Prevotella, which harbor genes for BCAA and histidine biosynthesis, contributed to decreased abundance of microbial genes involved in the biosynthesis of those EAAs in patients with HF.Conclusions: The present study demonstrated the relationship between gut microbiota and AA metabolic disturbances in patients with HF.
format article
author Tomohiro Hayashi
Tomohiro Hayashi
Tomoya Yamashita
Tomoya Takahashi
Tokiko Tabata
Hikaru Watanabe
Yasuhiro Gotoh
Masakazu Shinohara
Masakazu Shinohara
Kenjiro Kami
Hidekazu Tanaka
Kensuke Matsumoto
Tetsuya Hayashi
Takuji Yamada
Ken-ichi Hirata
author_facet Tomohiro Hayashi
Tomohiro Hayashi
Tomoya Yamashita
Tomoya Takahashi
Tokiko Tabata
Hikaru Watanabe
Yasuhiro Gotoh
Masakazu Shinohara
Masakazu Shinohara
Kenjiro Kami
Hidekazu Tanaka
Kensuke Matsumoto
Tetsuya Hayashi
Takuji Yamada
Ken-ichi Hirata
author_sort Tomohiro Hayashi
title Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
title_short Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
title_full Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
title_fullStr Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
title_full_unstemmed Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis
title_sort uncovering the role of gut microbiota in amino acid metabolic disturbances in heart failure through metagenomic analysis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e4bce4d3ccba4999961682680d432511
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