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Wang J, Yin J, Liu X, Liu Y, Jin X. Gut commensal bacterium Bacteroides vulgatus exacerbates helminth-induced cardiac fibrosis through succinate accumulation. PLoS Pathog 2025; 21:e1013069. [PMID: 40238740 PMCID: PMC12002503 DOI: 10.1371/journal.ppat.1013069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/21/2025] [Indexed: 04/18/2025] Open
Abstract
Trichinella spiralis (Ts) is known to cause cardiac fibrosis, which is a critical precursor to various heart diseases, and its progression is influenced by metabolic changes. However, the metabolic mechanisms remain unclear. Here, we observed that Ts-infected mice exhibited cardiac fibrosis along with elevated succinate levels in the heart using metabolomic analysis. Administration of succinate exacerbated fibrosis during Ts infection, while deficiency in succinate receptor 1 (Sucnr1) alleviated the condition, highlighting the role of the succinate-Sucnr1 axis in fibrosis development. Furthermore, metagenomics sequencing showed that Ts-infected mice had a higher abundance ratio of succinate-producing bacteria to succinate-consuming bacteria in the intestines. Notably, the succinate-producer Bacteroides vulgatus was enriched in Ts group. Oral supplementation with B. vulgatus aggravated Ts-induced cardiac fibrosis. In summary, our findings underscore the succinate-Sucnr1 axis as a critical pathway in helminth-induced cardiac fibrosis and highlight the potential of targeting this axis for therapeutic interventions. This study presents novel insights into the gut-heart axis, revealing innovative strategies for managing cardiovascular complications associated with helminth infections.
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Affiliation(s)
- Jiaqi Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
- College of Animal Sciences, Jilin University, Changchun, China
| | - Jiali Yin
- The Second Hospital of Jilin University, Changchun, China
| | - Xiaolei Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yi Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
- College of Food Science and Engineering, Jilin University, Changchun, China
| | - Xuemin Jin
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
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Abrignani V, Salvo A, Pacinella G, Tuttolomondo A. The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review. Int J Mol Sci 2024; 25:4942. [PMID: 38732161 PMCID: PMC11084172 DOI: 10.3390/ijms25094942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 04/25/2024] [Accepted: 04/28/2024] [Indexed: 05/13/2024] Open
Abstract
The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratios, lipids, and inflammation markers, and even prevents the development of fatal and nonfatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns over its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbiota.
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Affiliation(s)
- Vincenzo Abrignani
- Internal Medicine and Stroke Care Ward, University of Palermo, 90127 Palermo, Italy; (V.A.); (A.S.); (G.P.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
| | - Andrea Salvo
- Internal Medicine and Stroke Care Ward, University of Palermo, 90127 Palermo, Italy; (V.A.); (A.S.); (G.P.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
| | - Gaetano Pacinella
- Internal Medicine and Stroke Care Ward, University of Palermo, 90127 Palermo, Italy; (V.A.); (A.S.); (G.P.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
| | - Antonino Tuttolomondo
- Internal Medicine and Stroke Care Ward, University of Palermo, 90127 Palermo, Italy; (V.A.); (A.S.); (G.P.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
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Hamjane N, Mechita MB, Nourouti NG, Barakat A. Gut microbiota dysbiosis -associated obesity and its involvement in cardiovascular diseases and type 2 diabetes. A systematic review. Microvasc Res 2024; 151:104601. [PMID: 37690507 DOI: 10.1016/j.mvr.2023.104601] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/24/2023] [Accepted: 09/02/2023] [Indexed: 09/12/2023]
Abstract
INTRODUCTION Obesity is a complex, multifactorial disease caused by various factors. Recently, the role of the gut microbiota in the development of obesity and its complications has attracted increasing interest. PURPOSE This article focuses on the mechanisms by which gut microbiota dysbiosis induces insulin resistance, type 2 diabetes, and cardiovascular diseases linked to obesity, highlighting the mechanisms explaining the role of gut microbiota dysbiosis-associated inflammation in the onset of these pathologies. METHODS A systematic study was carried out to understand and summarize the published results on this topic. More than 150 articles were included in this search, including different types of studies, consulted by an online search in English using various electronic search databases and predefined keywords related to the objectives of our study. RESULTS We have summarized the data from the articles consulted in this search, and we have found a major gut microbiota alteration in obesity, characterized by a specific decrease in butyrate-producing bacteria and the production of metabolites and components that lead to metabolic impairments and affect the progression of various diseases associated with obesity through distinct signaling pathways, including insulin resistance, type 2 diabetes, and cardiovascular diseases (CVD). We have also focused on the major role of inflammation as a link between gut microbiota dysbiosis and obesity-associated metabolic complications by explaining the mechanisms involved. CONCLUSION Gut microbiota dysbiosis plays a crucial role in the development of various obesity-related metabolic abnormalities, among them type 2 diabetes and CVD, and represents a major challenge for chronic disease prevention and health. Indeed, the intestinal microbiota appears to be a promising target for the nutritional or therapeutic management of these diseases.
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Affiliation(s)
- Nadia Hamjane
- Research Team in Biomedical Genomics and Oncogenetics, Faculty of Sciences and Technology of Tangier, Abdelmalek Essaadi University, Morocco.
| | - Mohcine Bennani Mechita
- Research Team in Biomedical Genomics and Oncogenetics, Faculty of Sciences and Technology of Tangier, Abdelmalek Essaadi University, Morocco
| | - Naima Ghailani Nourouti
- Research Team in Biomedical Genomics and Oncogenetics, Faculty of Sciences and Technology of Tangier, Abdelmalek Essaadi University, Morocco
| | - Amina Barakat
- Research Team in Biomedical Genomics and Oncogenetics, Faculty of Sciences and Technology of Tangier, Abdelmalek Essaadi University, Morocco
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Wang J, Liu X, Sun R, Mao H, Liu M, Jin X. Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2. PLoS Pathog 2023; 19:e1011683. [PMID: 37788279 PMCID: PMC10547169 DOI: 10.1371/journal.ppat.1011683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/12/2023] [Indexed: 10/05/2023] Open
Abstract
Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.
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Affiliation(s)
- Jiaqi Wang
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Animal Sciences, Jilin University, Changchun, China
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiaolei Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Ruohang Sun
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Hanhai Mao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Mingyuan Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Xuemin Jin
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
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Tokarek J, Budny E, Saar M, Stańczak K, Wojtanowska E, Młynarska E, Rysz J, Franczyk B. Molecular Processes Involved in the Shared Pathways between Cardiovascular Diseases and Diabetes. Biomedicines 2023; 11:2611. [PMID: 37892985 PMCID: PMC10604380 DOI: 10.3390/biomedicines11102611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/17/2023] [Accepted: 09/18/2023] [Indexed: 10/29/2023] Open
Abstract
Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD-with the focus on the molecular mechanisms and the role of the microbiota.
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Affiliation(s)
- Julita Tokarek
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Emilian Budny
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Maciej Saar
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Kamila Stańczak
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Ewa Wojtanowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (K.S.); (E.W.)
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Cui H, Han S, Dai Y, Xie W, Zheng R, Sun Y, Xia X, Deng X, Cao Y, Zhang M, Shang H. Gut microbiota and integrative traditional Chinese and western medicine in prevention and treatment of heart failure. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 117:154885. [PMID: 37302262 DOI: 10.1016/j.phymed.2023.154885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/27/2023] [Accepted: 05/15/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND Heart failure (HF) is the terminal stage of multiple cardiovascular diseases, with high mortality and morbidity. More and more studies have proved that gut microbiota may play a role in the process of HF, which is expected to become a new therapeutic target. The combination of traditional Chinese and Western medicine has vast therapeutic potential of complementation against HF. PURPOSE This manuscript expounds on the research progress of mechanisms of gut microbiota participating in the occurrence and prognosis of HF and the role of integrative traditional Chinese and Western medicine from 1987 to 2022. The combination of traditional Chinese and Western medicine in the prevention and treatment of HF from the perspective of gut microbiota has been discussed. METHODS Studies focusing on the effects and their mechanisms of gut microbiota in HF and the role of integrative traditional Chinese and Western medicine were identified and summarized, including contributions from February 1987 until August 2022. The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases up to April 2023 by using the relevant keywords and operators. RESULTS A total of 34 articles were finally included in this review.16 RCTs and 13 basic researches, and 3 clinical research studies involving 7 relevant outcome indicators(cardiac function evaluation index, changes in gut microbiota, inflammatory factors, metabolites of gut microbiota, serum nutritional index protein, quality of life score, intestinal permeability and all-cause mortality). Compared with healthy controls, serum TNF-α and TMAO levels were significantly higher in patients with heart failure [MD = 5.77, 95%CI(4.97, 6.56), p < 0.0001; SMD = 1.92, 95%CI(1.70, 2.14), p < 0.0001]. Escherichia coli and Thick-walled bacteria increased significantly [SMD = -0.99, 95%CI(-1.38, -0.61), p < 0.0001, SMD = 2.58, 95%CI(2.23, 2.93), p < 0.0001];The number of bacteroides and lactobacillus decreased [SMD = -2.29, 95%CI(-2.54, -2.04), p < 0.0001; SMD = -1.55, 95%CI(-1.8, -1.3), p < 0.0001]. There was no difference in bifidobacterium [SMD = 0.16, 95%CI(-0.22, 0.54), p = 0.42]. In the published literature, it is not difficult to see that most of the results are studied and proved based on animal experiments or clinical trials, involving the cellular level, while the mechanism and mode of action of the molecular biology of traditional Chinese medicine are less elaborated, which is related to the characteristics of multi-components and multi-targets of traditional Chinese medicine. The above are the shortcomings of published literature, which can also be the direction of future research. CONCLUSION Heart failure patients have decreased beneficial bacteria such as Bacillus mimics and Lactobacillus in the intestinal flora and increased harmful flora like thick-walled flora. And increase the inflammatory response of the body and the expression of trimethylamine oxide (TMAO) in the serum. And The prevention and treatment of integrative traditional Chinese and Western medicine against heart failure based on gut microbiota and its metabolites is a promising research direction.
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Affiliation(s)
- Herong Cui
- Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Songjie Han
- Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yanan Dai
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Wei Xie
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Rui Zheng
- Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yang Sun
- Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiaofeng Xia
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xiaopeng Deng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Yaru Cao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Mei Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
| | - Hongcai Shang
- Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
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Fan Y, Liang L, Tang X, Zhu J, Mu L, Wang M, Huang X, Gong S, Xu J, Liu T, Zhang T. Changes in the gut microbiota structure and function in rats with doxorubicin-induced heart failure. Front Cell Infect Microbiol 2023; 13:1135428. [PMID: 37180435 PMCID: PMC10173310 DOI: 10.3389/fcimb.2023.1135428] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 04/11/2023] [Indexed: 05/16/2023] Open
Abstract
Objectives The rat model of heart failure (HF) induced by doxorubicin (DOX), a broad spectrum and highly effective chemotherapeutic anthracycline with high-affinity to myocardial tissue that causes severe dose-dependent irreversible cardiotoxicity has been widely recognized and applied in HF pathogenesis and drug therapy studies. The gut microbiota (GM) has attracted significant attention due to its potential role in HF, and research in this area may provide beneficial therapeutic strategies for HF. Considering the differences in the route, mode, and total cumulative dose of DOX administration used to establish HF models, the optimal scheme for studying the correlation between GM and HF pathogenesis remains to be determined. Therefore, focusing on establishing the optimal scheme, we evaluated the correlation between GM composition/function and DOX-induced cardiotoxicity (DIC). Methods Three schemes were investigated: DOX (at total cumulative doses of 12, 15 or 18 mg/kg using a fixed or alternating dose via a tail vein or intraperitoneal injection) was administered to Sprague Dawley (SD) for six consecutive weeks. The M-mode echocardiograms performed cardiac function evaluation. Pathological changes in the intestine were observed by H&E staining and in the heart by Masson staining. The serum levels of N-terminal pre-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by ELISA. The GM was analysed by 16S rRNA gene sequencing. Key findings Strikingly, based on the severity of cardiac dysfunction, there were marked differences in the abundance and grouping of GM under different schemes. The HF model established by tail vein injection of DOX (18 mg/kg, alternating doses) was more stable; moreover, the degree of myocardial injury and microbial composition were more consistent with the clinical manifestations of HF. Conclusions The model of HF established by tail vein injection of doxorubicin, administered at 4mg/kg body weight (2mL/kg) at weeks 1, 3 and 5, and at 2mg/kg body weight (1mL/kg) at weeks 2, 4 and 6, with a cumulative total dose of 18mg/kg, is a better protocol to study the correlation between HF and GM.
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Affiliation(s)
- Yawen Fan
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Lichang Liang
- Department of Preventive Treatment, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Xinzheng Tang
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Jinxian Zhu
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Lei Mu
- Department of Encephalopathy Diseases, Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, China
| | - Mengni Wang
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Xuecheng Huang
- Department of Spinal Surgery, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Shenglan Gong
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Jinghan Xu
- Department of Endocrinology, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Tianjiao Liu
- Department of Endocrinology, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Tianfeng Zhang
- Department of Cardiovascular Diseases, The Sixth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
- *Correspondence: Tianfeng Zhang,
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Yang W, Xia Z, Zhu Y, Tang H, Xu H, Hu X, Lin C, Jiang T, He P, Shen J. Comprehensive Study of Untargeted Metabolomics and 16S rRNA Reveals the Mechanism of Fecal Microbiota Transplantation in Improving a Mouse Model of T2D. Diabetes Metab Syndr Obes 2023; 16:1367-1381. [PMID: 37197060 PMCID: PMC10184852 DOI: 10.2147/dmso.s404352] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 05/02/2023] [Indexed: 05/19/2023] Open
Abstract
Background Fecal microbiota transplantation (FMT) has emerged as a new therapy targeting gastrointestinal microbiota for the treatment of a growing number of diseases in recent years. Previous studies have suggested that FMT may be a potential therapy for type 2 diabetes (T2D), but the underlying mechanism remains unclear. Therefore, in the present study, we aimed to investigate the role of FMT in T2D and its underlying mechanisms. Methods To induce T2D, mice were fed a high-fat diet and injected with low-dose streptozotocin (STZ) for four weeks. The mice were then randomly divided into four groups: control group (n = 7), T2D group (n = 7), metformin (MET)-treated group (n = 7), and FMT group (n = 7). The MET group was orally administered 0.2 g/kg MET, the FMT group was orally administered 0.3 mL of bacterial solution, and the other two groups were orally administered the same volume of saline for four weeks. Serum and fecal samples were collected for non-targeted metabolomics, biochemical indicators, and 16S rRNA sequencing, respectively. Results Our results demonstrated that FMT had a curative effect on T2D by ameliorating hyperlipidemia and hyperglycemia. Using 16S rRNA sequencing and serum untargeted metabolomic analysis, we found that FMT could restore the disorders of gastrointestinal microbiota in T2D mice. Moreover, corticosterone, progesterone, L-urobilin, and other molecules were identified as biomarkers after FMT treatment. Our bioinformatics analysis suggested that steroid hormone biosynthesis, arginine, proline metabolism, and unsaturated fatty acid biosynthesis could be potential regulatory mechanisms of FMT. Conclusion In summary, our study provides comprehensive evidence for the role of FMT in the treatment of T2D. FMT has the potential to become a promising strategy for the treatment of metabolic disorders, T2D, and diabetes-related complications.
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Affiliation(s)
- Wensu Yang
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Zhaoxin Xia
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Yi Zhu
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Hao Tang
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Huaming Xu
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Xinyi Hu
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Chunhui Lin
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Tong Jiang
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Pei He
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
| | - Jilu Shen
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 23001, People’s Republic of China
- Anhui Public Health Clinical Center Hefei, Anhui, 230012, People’s Republic of China
- Correspondence: Jilu Shen, Tel +86-15155152963, Email
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Wang J, Chen J, Li L, Zhang H, Pang D, Ouyang H, Jin X, Tang X. Clostridium butyricum and Bifidobacterium pseudolongum Attenuate the Development of Cardiac Fibrosis in Mice. Microbiol Spectr 2022; 10:e0252422. [PMID: 36318049 PMCID: PMC9769846 DOI: 10.1128/spectrum.02524-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/22/2022] [Indexed: 11/05/2022] Open
Abstract
Cardiac fibrosis is an integral aspect of every form of cardiovascular diseases, which is one of the leading causes of death worldwide. It is urgent to explore new effective drugs and treatments. In this paper, transverse aortic constriction (TAC)-induced cardiac fibrosis was significantly alleviated by a cocktail of antibiotics to clear the intestinal flora, indicating that the gut microbiota was associated with the disease process of cardiac fibrosis. We transplanted feces from sham-operated and TAC-treated mice to mice treated with a cocktail of antibiotics. We found that TAC-treated gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis, indicating that targeted probiotics and related metabolite intervention may restore a normal microenvironment for the treatment or prevention of cardiac fibrosis. We used 16S rRNA sequencing of fecal samples and discovered that butyric acid-producing bacteria and Bifidobacterium pseudolongum were the dominant bacteria in the group with the lowest degree of cardiac fibrosis. Moreover, we demonstrated that sodium butyrate prevented the development of cardiac fibrosis. The effect of Clostridium butyricum (butyric acid-producing bacteria) was better than that of B. pseudolongum on cardiac fibrosis. Surprisingly, the cocktail of two probiotics had a stronger ability than a single probiotic. In conclusion, therapies targeting the gut microbiota and metabolites such as probiotics present new strategies for treating cardiovascular disease. IMPORTANCE Cardiac fibrosis is a basic process in cardiac remodeling. It is related to almost all types of cardiovascular diseases (CVD) and has become an important global health problem. Basic research and a number of clinical studies have shown that myocardial fibrosis can be prevented and reversed to a certain extent. It is urgent to explore new effective drugs and treatments. We indicated a causal relationship between cardiac fibrosis and gut microbiota. Gut microbiota dysbiosis cannot cause cardiac fibrosis on its own. Interestingly, healthy fecal microbiota transplantation could alleviate cardiac fibrosis. According to our findings, the combined use of butyric acid-producing bacteria and B. pseudolongum can help prevent cardiac fibrosis. Therapies targeting the gut microbiota and metabolites, such as probiotics, represent new strategies for treating cardiovascular disease.
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Affiliation(s)
- Jiaqi Wang
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Jiahuan Chen
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Linquan Li
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Huanyu Zhang
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Daxin Pang
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Hongsheng Ouyang
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
| | - Xuemin Jin
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun China
| | - Xiaochun Tang
- College of Animal Sciences, Jilin University, Changchun, People’s Republic of China
- Chongqing Research Institute of Jilin University, Chongqing, People’s Republic of China
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10
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Qian B, Zhang K, Li Y, Sun K. Update on gut microbiota in cardiovascular diseases. Front Cell Infect Microbiol 2022; 12:1059349. [PMID: 36439214 PMCID: PMC9684171 DOI: 10.3389/fcimb.2022.1059349] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 10/25/2022] [Indexed: 11/11/2022] Open
Abstract
In recent years, due to the development and widespread utilization of metagenomic sequencing and metabolomics, the relationship between gut microbiota and human cardiovascular diseases (CVDs) has received extensive attention. A growing number of studies have shown a strong relationship between gut microbiota and CVDs, such as coronary atherosclerosis, hypertension (HTN) and heart failure (HF). It has also been revealed that intestinal flora-related metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFA) and bile acids (BAs), are also related to the development, prevention, treatment and prognosis of CVDs. In this review, we presented and summarized the recent findings on the relationship between gut microbiota and CVDs, and concluded several currently known gut microbiota-related metabolites and the occurrence and development of CVDs.
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Affiliation(s)
| | | | - Yuan Li
- *Correspondence: Kangyun Sun, ; Yuan Li,
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11
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Cianci R, Franza L, Borriello R, Pagliari D, Gasbarrini A, Gambassi G. The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies. Biomedicines 2022; 10:2712. [PMID: 36359233 PMCID: PMC9687270 DOI: 10.3390/biomedicines10112712] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/20/2022] [Accepted: 10/22/2022] [Indexed: 10/29/2023] Open
Abstract
Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the disease. In particular, in the forms with preserved ejection fraction or with only mildly reduced ejection fraction, some specific associations with chronic inflammatory diseases have been observed. Another interesting aspect that is worth considering is the role of microbiota modulation, in this context: given the importance of microbiota in the modulation of immune responses, it is possible that changes in its composition may somewhat influence the progression and even the pathogenesis of heart failure. In this narrative review, we aim to examine the relationship between immunity and heart failure, with a special focus on the role of microbiota in this pathological condition.
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Affiliation(s)
- Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
| | - Laura Franza
- Emergency Medicine Unit, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
| | - Raffaele Borriello
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
| | - Danilo Pagliari
- Medical Officer of the Carabinieri Corps, Health Service of the Carabinieri General Headquarters, 00197 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
| | - Giovanni Gambassi
- Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy
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12
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Khan I, Khan I, Usman M, Jianye Z, Wei ZX, Ping X, Zhiqiang L, Lizhe A. Analysis of the blood bacterial composition of patients with acute coronary syndrome and chronic coronary syndrome. Front Cell Infect Microbiol 2022; 12:943808. [PMID: 36268223 PMCID: PMC9577097 DOI: 10.3389/fcimb.2022.943808] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 09/13/2022] [Indexed: 11/30/2022] Open
Abstract
Emerging evidence revealed that the blood microbiota plays a role in several non-communicable diseases, including cardiovascular disease. However, the role of circulating microbes in atherosclerosis remains understudied. To test this hypothesis, we performed this study to investigate the microbial profile in the blood of Chines atherosclerosis volunteers. A total of seventy Acute Coronary Syndrome patients, seventy Chronic Coronary Syndrome patients, and seventy healthy individuals were examined using high-throughput Illumina Novaseq targeting the V3-V4 regions of the 16S rRNA gene. The relationship between atherosclerosis and blood microbiome, clinical variables, and their functional pathways were also investigated. Our study observed significantly higher alpha diversity indices (Chao1, p = 0.001, and Shannon, p = 0.004) in the acute coronary syndrome group compared with chronic coronary syndrome and healthy group, although a significantly lower alpha diversity was observed in the chronic coronary syndrome compared to acute coronary syndrome and healthy group. Beta diversity based on principal coordinate analysis demonstrated a major separation among the three groups. In addition, using linear discriminant analysis, a significant distinct taxon such as Actinobacteria _ phylum, and Staphylococcus_ genus in the healthy group; Firmicutes_ phylum, and Lactobacillus_ genus in the chronic coronary syndrome group, and Proteobacteria and Acidobacteriota _ phyla in acute coronary syndrome group were observed among three groups. Clusters of Orthologous Genes grouped and Kyoto Encyclopedia of Genes and Genomes pathways suggested a significant variation among all groups (p < 0.05). The blood microbiota analysis provides potential biomarkers for the detection of coronary syndromes in this population.
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Affiliation(s)
- Ikram Khan
- Department of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, China
- School of Stomatology, Northwest Minzu University, Lanzhou, China
| | - Imran Khan
- Department of Microbiology, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Muhammad Usman
- State Key Laboratory of Grassland Agro-ecosystem, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Ruler Affairs, College of Pastoral Agriculture Sciences and Technology, Lanzhou University, Lanzhou, China
| | - Zhou Jianye
- School of Stomatology, Northwest Minzu University, Lanzhou, China
| | - Zhang Xiao Wei
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou, China
| | - Xie Ping
- Department of Cardiology, Gansu Provincial Hospital, Lanzhou, China
| | - Li Zhiqiang
- School of Stomatology, Northwest Minzu University, Lanzhou, China
- *Correspondence: Li Zhiqiang, ; An Lizhe,
| | - An Lizhe
- Department of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, China
- *Correspondence: Li Zhiqiang, ; An Lizhe,
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13
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Mutalub YB, Abdulwahab M, Mohammed A, Yahkub AM, AL-Mhanna SB, Yusof W, Tang SP, Rasool AHG, Mokhtar SS. Gut Microbiota Modulation as a Novel Therapeutic Strategy in Cardiometabolic Diseases. Foods 2022; 11:2575. [PMID: 36076760 PMCID: PMC9455664 DOI: 10.3390/foods11172575] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/20/2022] [Accepted: 08/22/2022] [Indexed: 11/19/2022] Open
Abstract
The human gut harbors microbial ecology that is in a symbiotic relationship with its host and has a vital function in keeping host homeostasis. Inimical alterations in the composition of gut microbiota, known as gut dysbiosis, have been associated with cardiometabolic diseases. Studies have revealed the variation in gut microbiota composition in healthy individuals as compared to the composition of those with cardiometabolic diseases. Perturbation of host-microbial interaction attenuates physiological processes and may incite several cardiometabolic disease pathways. This imbalance contributes to cardiometabolic diseases via metabolism-independent and metabolite-dependent pathways. The aim of this review was to elucidate studies that have demonstrated the complex relationship between the intestinal microbiota as well as their metabolites and the development/progression of cardiometabolic diseases. Furthermore, we systematically itemized the potential therapeutic approaches for cardiometabolic diseases that target gut microbiota and/or their metabolites by following the pathophysiological pathways of disease development. These approaches include the use of diet, prebiotics, and probiotics. With the exposition of the link between gut microbiota and cardiometabolic diseases, the human gut microbiota therefore becomes a potential therapeutic target in the development of novel cardiometabolic agents.
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Affiliation(s)
- Yahkub Babatunde Mutalub
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
- Department of Clinical Pharmacology, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Monsurat Abdulwahab
- Department of Midwifery, College of Nursing Sciences, Abubakar Tafawa Balewa University Teaching Hospital, Bauchi 74027, Nigeria
| | - Alkali Mohammed
- Department of Medicine, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Aishat Mutalib Yahkub
- College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi 74027, Nigeria
| | - Sameer Badri AL-Mhanna
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Wardah Yusof
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Suk Peng Tang
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
| | - Aida Hanum Ghulam Rasool
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
| | - Siti Safiah Mokhtar
- Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia or
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14
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Khan I, Khan I, Kakakhel MA, Xiaowei Z, Ting M, Ali I, Fei Y, Jianye Z, Zhiqiang L, Lizhe A. Comparison of Microbial Populations in the Blood of Patients With Myocardial Infarction and Healthy Individuals. Front Microbiol 2022; 13:845038. [PMID: 35694288 PMCID: PMC9176212 DOI: 10.3389/fmicb.2022.845038] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 03/31/2022] [Indexed: 01/03/2023] Open
Abstract
Increased bacterial translocation in the gut and bloodstream infections are both major comorbidities of heart failure and myocardial infarction (MI). However, the alterations in the microbiome of the blood of patients with MI remain unclear. To test this hypothesis, we conducted this case-control study to explore the microbiota compositions in the blood of Chinese patients with MI. Using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of the 16S ribosomal RNA (rRNA) gene, the microbiota communities in the blood of 29 patients with MI and 29 healthy controls were examined. In addition, the relationship between the blood microbiome and clinical features of MI was investigated. This study revealed a significant reduction in alpha diversity (Shannon index) in the MI group compared with the healthy controls. Also, a significant difference was detected in the structure and richness between the patients with MI and healthy controls. The members of the phylum Actinobacteria, class Actinobacteria, order Bifdobacteriales, family Bifidobacteriaceae, and genus Bifidobacterium were significantly abundant in the MI group, while the members of the phylum Bacteroidetes, class Bacteroidia, and order Bacteroidales were significantly enriched in the healthy controls (p < 0.05). Moreover, the functional analysis revealed a significant variation between both groups. For instance, the enrichment of genes involved in the metabolism pathways of three amino acids decreased, that is, nucleotide transport and metabolism, coenzyme transport and metabolism, and lipid transport and metabolism, among others. Our study will contribute to a better knowledge of the microbiota of blood, which will further lead to improved MI diagnosis and therapy. Further study is needed to determine the role of the blood microbiota in human health and disease.
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Affiliation(s)
- Ikram Khan
- School of Life Sciences, Lanzhou University, Lanzhou, China
- School of Stomatology, Northwest Minzu University, Lanzhou, China
| | - Imran Khan
- Department of Microbiology, Khyber Medical University Peshawar, Peshawar, Pakistan
| | | | | | - Mao Ting
- Lanzhou University Second Hospital, Lanzhou, China
| | - Ikram Ali
- School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Yu Fei
- School of Stomatology, Northwest Minzu University, Lanzhou, China
| | - Zhou Jianye
- School of Stomatology, Northwest Minzu University, Lanzhou, China
| | - Li Zhiqiang
- School of Stomatology, Northwest Minzu University, Lanzhou, China
- *Correspondence: Li Zhiqiang
| | - An Lizhe
- School of Life Sciences, Lanzhou University, Lanzhou, China
- An Lizhe
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15
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Gut Microbiome and Organ Fibrosis. Nutrients 2022; 14:nu14020352. [PMID: 35057530 PMCID: PMC8781069 DOI: 10.3390/nu14020352] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/07/2022] [Accepted: 01/08/2022] [Indexed: 02/07/2023] Open
Abstract
Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.
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16
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Gallo A, Macerola N, Favuzzi AM, Nicolazzi MA, Gasbarrini A, Montalto M. The Gut in Heart Failure: Current Knowledge and Novel Frontiers. Med Princ Pract 2022; 31:203-214. [PMID: 35093952 PMCID: PMC9275003 DOI: 10.1159/000522284] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 01/23/2022] [Indexed: 11/22/2022] Open
Abstract
Heart failure (HF) represents a major health problem affecting millions of people worldwide. In the latest years, many efforts have been made to search for more effective strategies to prevent and modify the course of this disease, but results are still not satisfying. HF represents a complex clinical syndrome involving many other systems, including the gastrointestinal system. Although the relationship between the gut and HF is far from being fully understood, based on recent evidence highlighting the putative role of the gastrointestinal system in different cardiovascular diseases, it is conceivable that the gut-heart link may represent the basis for novel therapeutic approaches in the HF context as well. This intricate interplay involving typical hemodynamic changes and their consequences on gut morphology, permeability, and function, sets the stage for alterations in microbiota composition and is able to impact mechanisms of HF through different routes such as bacterial translocation and metabolic pathways. Thus, the modulation of the gut microbiota through diet, probiotics, and fecal transplantation has been suggested as a potential therapeutic approach. More interestingly, another effect of alteration in microbiota composition reflects in the upregulation of cotransporters (NHE3) with consequent salt and fluid overload and worsening visceral congestion. Therefore, the inhibitors of this cotransporter may also represent a novel therapeutic frontier. By review of recent data on this topic, we describe the current state of the complex interplay between the gastrointestinal and cardiac systems in HF, and the relevance of this knowledge in seeking new therapeutic strategies.
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Affiliation(s)
- Antonella Gallo
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- *Antonella Gallo,
| | - Noemi Macerola
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Angela Maria Favuzzi
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Maria Anna Nicolazzi
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Massimo Montalto
- Department of Medical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
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17
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Lv S, Wang Y, Zhang W, Shang H. Trimethylamine oxide: a potential target for heart failure therapy. Heart 2021; 108:917-922. [PMID: 34611047 DOI: 10.1136/heartjnl-2021-320054] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/09/2021] [Indexed: 11/04/2022] Open
Abstract
Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.
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Affiliation(s)
- Shichao Lv
- Key Laboratory of Chinese Internal Medicine of MOE, Dongzhimen Hospital, BUCM, Beijing, China.,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yunjiao Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wanqin Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hongcai Shang
- Key Laboratory of Chinese Internal Medicine of MOE, Dongzhimen Hospital, BUCM, Beijing, China
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18
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Gut Microbiome, Functional Food, Atherosclerosis, and Vascular Calcifications-Is There a Missing Link? Microorganisms 2021; 9:microorganisms9091913. [PMID: 34576810 PMCID: PMC8472650 DOI: 10.3390/microorganisms9091913] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/21/2021] [Accepted: 09/07/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiome is represented by the genome of all microorganisms (symbiotic, potential pathogens, or pathogens) residing in the intestine. These ecological communities are involved in almost all metabolic diseases and cardiovascular diseases are not excluded. Atherosclerosis, with a continuously increasing incidence in recent years, is the leading cause of coronary heart disease and stroke by plaque rupture and intraplaque hemorrhage. Vascular calcification, a process very much alike with osteogenesis, is considered to be a marker of advanced atherosclerosis. New evidence, suggesting the role of dietary intake influence on the diversity of the gut microbiome in the development of vascular calcifications, is highly debated. Gut microbiota can metabolize choline, phosphatidylcholine, and L-carnitine and produce vasculotoxic metabolites, such as trimethylamine-N-oxide (TMAO), a proatherogenic metabolite. This review article aims to discuss the latest research about how probiotics and the correction of diet is impacting the gut microbiota and its metabolites in the atherosclerotic process and vascular calcification. Further studies could create the premises for interventions in the microbiome as future primary tools in the prevention of atherosclerotic plaque and vascular calcifications.
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19
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Tsai HJ, Tsai WC, Hung WC, Hung WW, Chang CC, Dai CY, Tsai YC. Gut Microbiota and Subclinical Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus. Nutrients 2021; 13:nu13082679. [PMID: 34444839 PMCID: PMC8397936 DOI: 10.3390/nu13082679] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 01/14/2023] Open
Abstract
Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.
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Affiliation(s)
- Hui-Ju Tsai
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan;
- Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Wei-Chung Tsai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Wei-Chun Hung
- Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-C.H.); (C.-C.C.)
| | - Wei-Wen Hung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Chen-Chia Chang
- Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-C.H.); (C.-C.C.)
| | - Chia-Yen Dai
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yi-Chun Tsai
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Liquid Biopsy and Cohort Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7-3121101-5029; Fax: +886-7-3122810
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Anselmi G, Gagliardi L, Egidi G, Leone S, Gasbarrini A, Miggiano GAD, Galiuto L. Gut Microbiota and Cardiovascular Diseases: A Critical Review. Cardiol Rev 2021; 29:195-204. [PMID: 32639240 DOI: 10.1097/crd.0000000000000327] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The human intestine contains the largest and most diverse ecosystem of microbes. The main function of the intestinal bacterial flora is to limit the growth of potentially pathogenic microorganisms. However, the intestinal microbiota is increasingly emerging as a risk factor for the development of cardiovascular disease (CVD). The gut microbiota-derived metabolites, such as short-chain fatty acids, trimethylamine-N-oxide, bile acids, and polyphenols play a pivotal role in maintaining healthy cardiovascular function, and when dysregulated, can potentially lead to CVD. In particular, changes in the composition and diversity of gut microbiota, known as dysbiosis, have been associated with atherosclerosis, hypertension, and heart failure. Nonetheless, the underlying mechanisms remain yet to be fully understood. Therefore, the microbiota and its metabolites have become a new therapeutic target for the prevention and treatment of CVD. In addition to a varied and balanced diet, the use of prebiotic and probiotic treatments or selective trimethylamine-N-oxide inhibitors could play a pivotal role in the prevention of CVD, especially in patients with a high metabolic risk.
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Affiliation(s)
- Gaia Anselmi
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Lucilla Gagliardi
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gabriele Egidi
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Sabrina Leone
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- UOC di Medicina Interna e Gastroenterologia, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giacinto Abele Donato Miggiano
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Leonarda Galiuto
- From the UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
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Moludi J, Saiedi S, Ebrahimi B, Alizadeh M, Khajebishak Y, Ghadimi SS. Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: a Single-Center Double-Blind Clinical Study. J Cardiovasc Transl Res 2021; 14:299-307. [PMID: 32681453 DOI: 10.1007/s12265-020-10052-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/14/2020] [Indexed: 12/16/2022]
Abstract
Adverse cardiac remodeling after myocardial infarction (MI) can lead to the syndrome of heart failure (HF). Recently, changes in gut microbiota composition (dysbiosis) have appeared as a novel candidate that may be linked to the development of CR and HF. The aim of this trial was to evaluate the effects of probiotics administration on attenuating CR in patients with MI. A single-center double-blind placebo-controlled stratified randomized clinical study was conducted in 44 subjects with MI who underwent percutaneous coronary intervention (PCI). Patients were randomly assigned to take, with lunch, either a probiotic capsule containing 1.6 × 109 colony-forming unit (CFU) of bacteria (treatment group) or capsules contained inulin (control group) over 3 months. CR biomarkers (including serum procollagen III, transforming growth factor beta (TGF-β), trimethylamine N-oxide (TMAO), and matrix metallopeptidase 9 (MMP-9)) were assessed. Echocardiography results were measured at baseline and after the intervention. Significant decreases were seen in serum TGF-β concentrations (- 8.0 ± 2.1 vs. - 4.01 ± 1.8 pg/mL, p = 0.001) and TMAO levels (- 17.43 ± 10.20 vs. - 4.54 ± 8.7 mmol/L, p = 0.043), and there were no differences were seen in MMP-9 (- 4.1 ± 0.12 vs. - 4.01 + 0.15 nmol/mL, p = 0.443) and procollagen III levels (- 1.35 ± 0.70 vs. 0.01 + 0.3 mg/L, p = 0.392) subsequent to probiotics supplementation compared with the placebo group. Improvements in echocardiographic indices were also greater in the probiotics group as compared with that in the control group, but not at a significant level. Regression analysis revealed that baseline left ventricular ejection fraction (LVEF), and changes of procollagen III, predicted 62% of the final LVEF levels. Probiotics administration may have a beneficial effect on the cardiac remodeling process in patients with myocardial infarction. Iranian Registry of Clinical Trials (IRCT): IRCT20121028011288N15.
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Affiliation(s)
- Jalal Moludi
- School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Somaieh Saiedi
- Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Alizadeh
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | | | - Sevda Saleh Ghadimi
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Heart-gut axis: Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to prevent cardiovascular disease through gut microbiota. MEDICINE IN MICROECOLOGY 2021. [DOI: 10.1016/j.medmic.2021.100033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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23
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Song T, Guan X, Wang X, Qu S, Zhang S, Hui W, Men L, Chen X. Dynamic modulation of gut microbiota improves post-myocardial infarct tissue repair in rats via butyric acid-mediated histone deacetylase inhibition. FASEB J 2021; 35:e21385. [PMID: 33565193 DOI: 10.1096/fj.201903129rrr] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 01/03/2021] [Accepted: 01/07/2021] [Indexed: 02/02/2023]
Abstract
The complex and dynamic population of gut microbiota exerts a marked influence on the host during homeostasis and disease. Imbalance of gut microbiota metabolites may lead to cardiac dysfunction in patients with heart failure, which is related to myocardial infarction(MI) severity. However, the role of gut microbiota in the repair process after MI has rarely been reported. To explore the role of gut microbiota in MI repair and its underlying mechanism, we mixed antibiotics in drinking water to interfere with gut microbiota in rats. Hematoxylin and eosin staining, Sirius red staining, western blotting, and immunohistochemistry were used to detect tissue repair and fibrosis. We found that the expressions of alpha-smooth muscle actin, collagen, and histone deacetylase (HDAC) activities were significantly increased. We detected gut microbiota at different time points after MI using 16S ribosomal RNA sequencing and detected that Prevotellaceae, Clostridiaceae, and Lachnospiraceae were significantly altered among the butyric acid producers. We administered sodium butyrate via drinking water and discovered that sodium butyrate reduced HDAC activities and adverse repair. Therefore, we speculated that gut microbiota influences the acetylation level and tissue repair process after MI by affecting butyric acid production.
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Affiliation(s)
- Tongtong Song
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Xin Guan
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Xuan Wang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Shanshan Qu
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Siwei Zhang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Wenting Hui
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Lihui Men
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Xia Chen
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China
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Implication of Gut Microbiota in Cardiovascular Diseases. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5394096. [PMID: 33062141 PMCID: PMC7533754 DOI: 10.1155/2020/5394096] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 07/13/2020] [Accepted: 07/16/2020] [Indexed: 12/14/2022]
Abstract
Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.
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Abstract
We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1-5 µm levels implied in some TMAO-CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.
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Cross-Talk between Gut Microbiota and the Heart: A New Target for the Herbal Medicine Treatment of Heart Failure? EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9097821. [PMID: 32328141 PMCID: PMC7165350 DOI: 10.1155/2020/9097821] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/19/2020] [Accepted: 02/05/2020] [Indexed: 02/06/2023]
Abstract
Heart failure (HF) is the severe and terminal stage of various heart diseases. A growing number of studies have suggested the potential clinical significance of gut microbiota in the pathophysiology of HF. Herbal medicine (HM) plays a role in rebalancing the composition of gut microbiota and is widely used in the prevention and treatment of HF. There are many similarities between intestinal microecology and the traditional Chinese medicine (TCM) theory, such as the holistic concept and the theory of the “heart's connection with the small intestine.” These similarities provide a theoretical basis for HM to prevent and treat diseases by regulating the intestinal flora and its metabolites. In this work, the cross-talk between gut microbiota and the heart is reviewed, and the relationship between TCM and gut microbiota is discussed. Based on the current literature and research, we hypothesize that the cross-talk between gut microbiota and the heart may offer a new therapeutic target for HF intervention.
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27
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Yuzefpolskaya M, Bohn B, Nasiri M, Zuver AM, Onat DD, Royzman EA, Nwokocha J, Mabasa M, Pinsino A, Brunjes D, Gaudig A, Clemons A, Trinh P, Stump S, Giddins MJ, Topkara VK, Garan AR, Takeda K, Takayama H, Naka Y, Farr MA, Nandakumar R, Uhlemann AC, Colombo PC, Demmer RT. Gut microbiota, endotoxemia, inflammation, and oxidative stress in patients with heart failure, left ventricular assist device, and transplant. J Heart Lung Transplant 2020; 39:880-890. [PMID: 32139154 DOI: 10.1016/j.healun.2020.02.004] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 01/13/2020] [Accepted: 02/06/2020] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I-IV), LVAD, and HT. METHODS We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing. RESULTS Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p < 0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p < 0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I-III) as well as in patients with LVAD and HT (p < 0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I-III, p < 0.05) but not in patients with HT. CONCLUSIONS Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT.
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Affiliation(s)
- Melana Yuzefpolskaya
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Bruno Bohn
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - Mojdeh Nasiri
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Amelia M Zuver
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Drew D Onat
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Eugene A Royzman
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Joseph Nwokocha
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Melissa Mabasa
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Alberto Pinsino
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Danielle Brunjes
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Antonia Gaudig
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Autumn Clemons
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Pauline Trinh
- Department of Environmental and Occupational Health Sciences, University of Washington, School of Public Health, Seattle, Washington
| | - Stephania Stump
- Department of Medicine, Division of Infectious Diseases and Microbiome and Pathogen Genomics Core, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Marla J Giddins
- Department of Medicine, Division of Infectious Diseases and Microbiome and Pathogen Genomics Core, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Veli K Topkara
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - A Reshad Garan
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Koji Takeda
- Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Hiroo Takayama
- Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Yoshifumi Naka
- Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Maryjane A Farr
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Renu Nandakumar
- Biomarkers Core Laboratory, Irving Institute for Clinical and Translational Research, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Anne-Catrin Uhlemann
- Department of Medicine, Division of Infectious Diseases and Microbiome and Pathogen Genomics Core, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Paolo C Colombo
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York
| | - Ryan T Demmer
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; Division of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York.
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Formiga F, Ferreira Teles CI, Chivite D. Impact of intestinal microbiota in patients with heart failure: A systematic review. Med Clin (Barc) 2019; 153:402-409. [PMID: 31416611 DOI: 10.1016/j.medcli.2019.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 06/21/2019] [Accepted: 06/22/2019] [Indexed: 10/26/2022]
Abstract
Heart failure (HF) is a chronic disease with significant morbidity and mortality. Substantial haemodynamic changes such as hypoperfusion and intestinal congestion can alter the composition of the intestinal microbiota in patients with HF. The aim of this systematic review is to evaluate the influence of bowel function in patients with HF and the possible role of the intestinal microbiota in the development and evolution of the latter. Eleven studies were included in the review. These studies seem to confirm that HF patients present with substantial abnormalities in the composition of their intestinal microbiota. Trimethylamine N-oxide is identified as a key mediator between the alterations in the intestinal microbiota and HF and correlates with worse prognosis in HF patients. In conclusion, patients with HF present with frequent abnormalities in the characteristics of their intestinal microbiota, which may play a role in the prognosis of the disease.
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Affiliation(s)
- Francesc Formiga
- Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, España.
| | - Cristiana Isabel Ferreira Teles
- Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, España
| | - David Chivite
- Servicio de Medicina Interna, Hospital Universitario de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, España
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Prevention and treatment of chronic heart failure through traditional Chinese medicine: Role of the gut microbiota. Pharmacol Res 2019; 151:104552. [PMID: 31747557 DOI: 10.1016/j.phrs.2019.104552] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 10/31/2019] [Accepted: 11/16/2019] [Indexed: 12/17/2022]
Abstract
In recent years, although the concept and means of modern treatment of chronic heart failure(CHF) are continually improving, the readmission rate and mortality rate are still high. At present, there is evidence that there is a link between gut microbiota and heart failure, so the intervention of gut microbiota and its metabolites is expected to become a potential new therapeutic target in heart failure. Traditional Chinese medicine(TCM) has apparent advantages in stabilizing the disease, improving heart function, and improving the quality of life. It can exert its effect by operating in the gut microbiota and is an ideal intestinal micro-ecological regulator. Therefore, this article will mainly discuss the advantages of traditional Chinese medicine in treating CHF, the relationship between traditional Chinese medicine and gut microbiota, the relationship between CHF and gut microbiota, and the ways of regulating gut microbiota by traditional Chinese medicine to prevent and treat CHF. It will specify the target and mechanism of traditional Chinese medicine treating heart failure by acting gut microbiota and provide ideas for the treatment of heart failure.
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30
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Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure. Cardiovasc Ther 2019; 2019:5164298. [PMID: 31819762 PMCID: PMC6885196 DOI: 10.1155/2019/5164298] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 09/16/2019] [Accepted: 09/19/2019] [Indexed: 12/11/2022] Open
Abstract
Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.
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31
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Cresci S, Pereira NL, Ahmad F, Byku M, de las Fuentes L, Lanfear DE, Reilly CM, Owens AT, Wolf MJ. Heart Failure in the Era of Precision Medicine: A Scientific Statement From the American Heart Association. CIRCULATION. GENOMIC AND PRECISION MEDICINE 2019; 12:458-485. [PMID: 31510778 DOI: 10.1161/hcg.0000000000000058] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
One of 5 people will develop heart failure over his or her lifetime. Early diagnosis and better understanding of the pathophysiology of this disease are critical to optimal treatment. The "omics"-genomics, pharmacogenomics, epigenomics, proteomics, metabolomics, and microbiomics- of heart failure represent rapidly expanding fields of science that have, to date, not been integrated into a single body of work. The goals of this statement are to provide a comprehensive overview of the current state of these omics as they relate to the development and progression of heart failure and to consider the current and potential future applications of these data for precision medicine with respect to prevention, diagnosis, and therapy.
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32
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Amar J, Lelouvier B, Servant F, Lluch J, Burcelin R, Bongard V, Elbaz M. Blood Microbiota Modification After Myocardial Infarction Depends Upon Low-Density Lipoprotein Cholesterol Levels. J Am Heart Assoc 2019; 8:e011797. [PMID: 31566105 PMCID: PMC6806051 DOI: 10.1161/jaha.118.011797] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background The role of bacteria on the onset of cardiovascular disease has been suggested. Reciprocally, increased intestinal bacterial translocation and bloodstream infection are common comorbidities associated with heart failure and myocardial infarction (MI). In this context, the aim of this study was to analyze the blood microbiome in patients shortly after acute myocardial infarction. Methods and Results We carried out a case control study comparing 103 patients at high cardiovascular risk but free of coronary disease and 99 patients who had an MI. The blood microbiome was analyzed both quantitatively by 16S quantitative polymerase chain reaction and qualitatively by 16S targeted metagenomic sequencing specifically optimized for blood samples. A significant increase in blood bacterial 16S rDNA concentration was observed in patients admitted for MI. This increase in blood bacterial DNA concentration was independent of post‐MI left ventricular function and was more marked in patients with low‐density lipoprotein cholesterol ≥1 g/L. In addition, differences in the proportion of numerous bacterial taxa in blood were significantly modified with the onset of MI, thus defining a blood microbiota signature of MI. Among the bacterial taxa whose proportions are decreased in patients with MI, at least 6 are known to include species able to metabolize cholesterol. Conclusions These results could provide the basis for the identification of blood microbiome‐based biomarkers for the stratification of MI patients. Furthermore, these findings should provide insight into the mechanism underlying the negative correlation reported between low‐density lipoprotein cholesterol concentration and the prognosis at the acute onset of MI and mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02405468.
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Affiliation(s)
- Jacques Amar
- Vaiomer Labège France.,Department of Therapeutics Rangueil Hospital CHU Toulouse Toulouse France.,INSERM U1048 I2MC Toulouse France
| | | | | | | | - Rémy Burcelin
- Vaiomer Labège France.,INSERM U1048 I2MC Toulouse France
| | - Vanina Bongard
- Epidemiology Department Rangueil Hospital CHU Toulouse Toulouse France.,Toulouse 3 Paul Sabatier University Toulouse France.,INSERM UMR 1027 Toulouse France
| | - Meyer Elbaz
- Metabolic and Cardiovascular Diseases Department Rangueil Hospital CHU Toulouse Toulouse France.,INSERM U1048 I2MC Toulouse France
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Ahmad AF, Dwivedi G, O'Gara F, Caparros-Martin J, Ward NC. The gut microbiome and cardiovascular disease: current knowledge and clinical potential. Am J Physiol Heart Circ Physiol 2019; 317:H923-H938. [PMID: 31469291 DOI: 10.1152/ajpheart.00376.2019] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.
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Affiliation(s)
- Adilah F Ahmad
- Medical School, University of Western Australia, Perth, Western Australia, Australia.,Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia
| | - Girish Dwivedi
- Medical School, University of Western Australia, Perth, Western Australia, Australia.,Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.,Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Fergal O'Gara
- School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Western Australia, Australia.,Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.,BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland.,Telethon Kids Institute, Children's Hospital, Perth, Western Australia, Australia
| | - Jose Caparros-Martin
- School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Western Australia, Australia.,Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - Natalie C Ward
- Medical School, University of Western Australia, Perth, Western Australia, Australia.,School of Public Health, Curtin University, Perth Western Australia, Australia
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Chen X, Li HY, Hu XM, Zhang Y, Zhang SY. Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure. Chin Med J (Engl) 2019; 132:1843-1855. [PMID: 31306229 PMCID: PMC6759126 DOI: 10.1097/cm9.0000000000000330] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed. DATA SOURCES This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation." RESULTS Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure. CONCLUSIONS The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.
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Affiliation(s)
- Xi Chen
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Han-Yu Li
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao-Min Hu
- Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yan Zhang
- State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China
| | - Shu-Yang Zhang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Specialized Pro-resolving Mediators Directs Cardiac Healing and Repair with Activation of Inflammation and Resolution Program in Heart Failure. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1161:45-64. [PMID: 31562621 DOI: 10.1007/978-3-030-21735-8_6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
After myocardial infarction, splenic leukocytes direct biosynthesis of specialized pro-resolving mediators (SPMs) that are essential for the resolution of inflammation and tissue repair. In a laboratory environment, after coronary ligation of healthy risk free rodents (young adult mice) leukocytes biosynthesize SPMs with induced activity of lipoxygenases and cyclooxygenases, which facilitate cardiac repair. Activated monocytes/macrophages drive the biosynthesis of SPMs following experimental myocardial infarction in mice during the acute heart failure. In the presented review, we provided the recent updates on SPMs (resolvins, lipoxins and maresins) in cardiac repair that may serve as novel therapeutics for future heart failure therapy/management. We incorporated the underlying causes of non-resolving inflammation following cardiac injury if superimposed with obesity, hypertension, diabetes, disrupted circadian rhythm, co-medication (painkillers or oncological therapeutics), and/or aging that may delay or impair the biosynthesis of SPMs, intensifying pathological remodeling in heart failure.
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Myocardial infarction and gut microbiota: An incidental connection. Pharmacol Res 2018; 129:308-317. [DOI: 10.1016/j.phrs.2017.11.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 11/05/2017] [Accepted: 11/09/2017] [Indexed: 02/06/2023]
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Liu Z, Liu HY, Zhou H, Zhan Q, Lai W, Zeng Q, Ren H, Xu D. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice. Front Microbiol 2017; 8:1687. [PMID: 28919891 PMCID: PMC5585143 DOI: 10.3389/fmicb.2017.01687] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 08/21/2017] [Indexed: 12/20/2022] Open
Abstract
Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.
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Affiliation(s)
- Zuheng Liu
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
| | - Hai-Yue Liu
- Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China.,Department of Environmental Health, School of Public Health, Southern Medical UniversityGuangzhou, China
| | - Haobin Zhou
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
| | - Qiong Zhan
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
| | - Wenyan Lai
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
| | - Qingchun Zeng
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
| | - Hao Ren
- Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China.,Department of Rheumatology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China
| | - Dingli Xu
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, China.,Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of ChinaGuangzhou, China
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