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

Hayashi, Tomohiro; Yamashita, Tomoya; Takahashi, Tomoya; Tabata, Toshihide; Watanabe, Hikaru; Gotoh, Yasuhiro; Shinohara, Masakazu; Kami, Kenjiro; Tanaka, Hidekazu; Matsumoto, Kensuke; Hayashi, Tetsuya; Yamada, Takuji; Hirata, Ken‐ichi

doi:10.3389/fcvm.2021.789325

Cited by 26 publications

(22 citation statements)

References 51 publications

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“…It is demonstrated that a significant positive correlation between the abundance of microbial genes involved in branched-chain AAs (BCAAs) biosynthesis and plasma BCCA levels in patients with HF. 11 It is interesting to discover that dapagliflozin enriched the valine and isoleucine in serum in our study, which is consistent with the result that empagliflozin switches myocardial fuel utilization away from glucose toward BCAA, thereby enhancing LV systolic function, and ameliorating adverse LV remodelling. 12 Moreover, compared with the Sham and the MI group, dapagliflozin treatment influenced the diversities and composition of faecal microbiota.…”

Section: Discussionsupporting

confidence: 88%

“…The branched‐chain amino acid (BCAA) abnormalities serve as predictors of adverse outcomes in patients with HF, T2DM, and insulin resistance. It is demonstrated that a significant positive correlation between the abundance of microbial genes involved in branched‐chain AAs (BCAAs) biosynthesis and plasma BCCA levels in patients with HF 11 . It is interesting to discover that dapagliflozin enriched the valine and isoleucine in serum in our study, which is consistent with the result that empagliflozin switches myocardial fuel utilization away from glucose toward BCAA, thereby enhancing LV systolic function, and ameliorating adverse LV remodelling 12 …”

Section: Discussionsupporting

confidence: 81%

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Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice

Wang

Ding

et al. 2022

Clin Exp Pharma Physio

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The gut microbiota seems to be a major modulator of cardiovascular diseases, such as myocardial infarction. Dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), is an antidiabetic agent that was recently utilized in patients with cardiovascular diseases. This study aims to investigate the effects of dapagliflozin on the faecal microbiota of postinfarction non‐diabetic mice. A total of 19 male mice were randomly divided into three groups, where two groups were enduced with myocardial infarction (MI) by left anterior descending ligation. One day after the surgery, each group was administered normal saline (15 mL/kg/day, 0.9%) or dapagliflozin (1.5 mg/kg/day) for 4 weeks. Echocardiography was obtained on day 28 post MI. Masson's trichrome staining was used to determine the degree of fibrosis. Faecal samples were collected to assess the microbiome by 16S ribosomal RNA gene sequencing. We found that dapagliflozin significantly improved cardiac function in the non‐diabetic myocardial infarction mice model after the 28‐day treatment, especially in ejection fraction and fractional shortening (p < 0.01). Enterotypes were composed of Muribaculaceae and Lactobacillaceae after dapagliflozin treatment, while Muribaculaceae and Erysipelotrichaceae were the main enterotypes post‐MI. Dapagliflozin increased the abundance of beneficial bacteria like Lactobacillaceae, while decreasing the abundance of beneficial bacteria like Bifidobacteriaceae. It was interesting to discover that Proteobacteria (especially Desulfovibrionaceae) were enriched after the dapagliflozin treatment for myocardial infarction. Dapagliflozin increased the abundance of the main beneficial bacteria. In post‐myocardial infarction treatments, using dapagliflozin could positively contribute to the improvement of cardiac function and alter the structure of faecal microbiota.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 81%

Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice

Wang

Ding

et al. 2022

Clin Exp Pharma Physio

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“…Patients with heart failure have lower plasma essential amino acid levels than healthy controls. The lack of Eubacterium and Prevotella leads to the decreased biosynthesis of essential amino acids (especially BCAAs and histidine) in patients with heart failure, on account of the reduced abundance of microbial genes related to essential amino acid biosynthesis ( 27 ). Prevotella-copri is lipopolysaccharide-producing bacteria, making it related to low-grade inflammation and the synthesis of BCAAs ( 28 ).…”

Section: Microbiota and Branched-chain Amino Acid-associated Metaboli...mentioning

confidence: 99%

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Liu

Yang

et al. 2022

Front. Nutr.

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Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential amino acids in human physiology. Decades of studies have revealed their roles in protein synthesis, regulating neurotransmitter synthesis, and the mechanistic target of rapamycin (mTOR). BCAAs are found to be related to many metabolic disorders, such as insulin resistance, obesity, and heart failure. Also, many diseases are related to the alteration of the BCAA catabolism enzyme branched-chain α-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, human autism with epilepsy, and so on. In this review, diseases and the corresponding therapies are discussed after the introduction of the catabolism and detection methods of BCAAs and BCKDK. Also, the interaction between microbiota and BCAAs is highlighted.

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“…In addition, the patients were not classified according to the type of heart failure, i.e., systolic or diastolic. Although a prior study conducted by Hayashi et al has refuted the role of ejection fraction in dysbiosis, further large-scale longitudinal studies are needed to exclude the effect of LVEF% on gut dysbiosis [26].…”

Section: Studies Involving Patients With Systolic and Diastolic Heart...mentioning

confidence: 99%

Re-defining the Gut Heart Axis: A Systematic Review of the Literature on the Role of Gut Microbial Dysbiosis in Patients With Heart Failure

Desai¹,

Desai²,

Jamil³

et al. 2023

Cureus

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Heart failure (HF) contributes to the cardiovascular health burden worldwide. Patients with heart failure have been recently studied to possess unique changes in the gut microbiome that affect immune homeostasis and metabolism. In this systematic review of the literature, we aim to identify the impact of gut dysbiosis on heart failure. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct our systematic review. We searched the literature on databases such as PubMed, PubMed Central (PMC), Medline, and ScienceDirect. Ten articles were included for review. There were significant differences in the gut microbiome composition in heart failure. Relative abundance of Ruminococcus gnavus, Escherichia Shigella, Streptococcus sp, Veillonella sp, and Actinobacteria, and relative depletion of Eubacterium, Prevotella, Faecalibacterium, SMB53, and Megamonas. The composition varied according to age, heart failure stage, and decompensation level. The composition remained unaltered with ejection fraction. There was an increased expression of genes responsible for the metabolism of amino acids, carbohydrates, choline trimethylamine-lyase (TMA-lyase), lipopolysaccharide (LPS) biosynthesis, tryptophan, and lipid metabolism. The resultant changes affected the levels of metabolites, such as trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and LPS, and inflammatory markers in the feces and plasma, which contributed to heart failure. These biomarkers of heart failure could serve as targets for the prevention and treatment of heart failure. Patients with heart failure harbor a unique constellation of gut microbiota that affect the pathogenesis of heart failure. Further studies are needed to understand the causal relationship between dysbiosis and heart failure.

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

Cited by 26 publications

References 51 publications

Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice

Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice

The Role of Branched-Chain Amino Acids and Branched-Chain α-Keto Acid Dehydrogenase Kinase in Metabolic Disorders

Re-defining the Gut Heart Axis: A Systematic Review of the Literature on the Role of Gut Microbial Dysbiosis in Patients With Heart Failure

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