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Yu Z, Guo M, Bai X, Ruan G, Sun Y, Han W, Yang H. Exploring the association between cardiovascular health and bowel health. Sci Rep 2024; 14:11819. [PMID: 38783080 PMCID: PMC11116406 DOI: 10.1038/s41598-024-62715-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 05/21/2024] [Indexed: 05/25/2024] Open
Abstract
Chronic constipation, diarrhea, and fecal incontinence have high incidence, potential disability, and socioeconomic impact, imposing a heavy burden on the quality of life. We aim to explore the association between cardiovascular health (CVH) and bowel health from National Health and Nutrition Survey 2005-2010. CVH is assessed using Life's Essential 8 (LE8). Chronic constipation, chronic diarrhea, and fecal incontinence are assessed based on Bristol Stool Form Scale classification, bowel movements, and bowel leakage. Better health behaviors (odds ratio [OR]: 0.71, 95% confidence interval [CI] 0.53-0.94, p = 0.02) and worse health factors (OR: 1.45, CI 1.03-2.04, p = 0.04) were associated with less chronic constipation. Less chronic diarrhea is correlated with better CVH (OR: 0.53, 95% CI 0.35-0.79, p = 0.003) and health factors (OR: 0.61, CI 0.46-0.81, p = 0.001). Meanwhile, the proportion of chronic diarrhea significantly decreases when the health behaviors score exceeds 59.42. Lower fecal incontinence was associated with better health behaviors (OR: 0.63, CI 0.44-0.90, p = 0.01) CVH. Better CVH and health behaviors are both linked to lower all-cause mortality in participants with chronic constipation and chronic diarrhea. A higher health behaviors score is also associated with less all-cause mortality in patients with fecal incontinence. Maintaining CVH at the population level contributes to intestinal health, achieving the dual management of both while saving on healthcare costs. However, further prospective research is needed to confirm these associations.
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Affiliation(s)
- Ziqing Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Yinghao Sun
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
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Guimarães VHD, Marinho BM, Motta-Santos D, Mendes GDRL, Santos SHS. Nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome. J Nutr Biochem 2023; 113:109252. [PMID: 36509338 DOI: 10.1016/j.jnutbio.2022.109252] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 11/12/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022]
Abstract
Obesity and metabolic disorders represent a significant global health problem and the gut microbiota plays an important role in modulating systemic homeostasis. Recent evidence shows that microbiota and its signaling pathways may affect the whole metabolism and the Renin-Angiotensin System (RAS), which in turn seems to modify microbiota. The present review aimed to investigate nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome components. A description of metabolic changes was obtained based on relevant scientific literature. The molecular and physiological mechanisms that impact the human microbiome were addressed, including the gut microbiota associated with obesity, diabetes, and hepatic steatosis. The RAS interaction signaling and modulation were analyzed. Strategies including the use of prebiotics, symbiotics, probiotics, and biotechnology may affect the gut microbiota and its impact on human health.
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Affiliation(s)
- Victor Hugo Dantas Guimarães
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil
| | - Barbhara Mota Marinho
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil
| | - Daisy Motta-Santos
- School of Physical Education, Physiotherapy, and Occupational Therapy - EEFFTO, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
| | - Gabriela da Rocha Lemos Mendes
- Food Engineering, Institute of Agricultural Sciences (ICA), Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Sérgio Henrique Sousa Santos
- Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil; Food Engineering, Institute of Agricultural Sciences (ICA), Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil.
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3
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Hypertension and renal disease programming: focus on the early postnatal period. Clin Sci (Lond) 2022; 136:1303-1339. [PMID: 36073779 DOI: 10.1042/cs20220293] [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: 05/09/2022] [Revised: 08/18/2022] [Accepted: 08/25/2022] [Indexed: 11/17/2022]
Abstract
The developmental origin of hypertension and renal disease is a concept highly supported by strong evidence coming from both human and animal studies. During development there are periods in which the organs are more vulnerable to stressors. Such periods of susceptibility are also called 'sensitive windows of exposure'. It was shown that as earlier an adverse event occurs; the greater are the consequences for health impairment. However, evidence show that the postnatal period is also quite important for hypertension and renal disease programming, especially in rodents because they complete nephrogenesis postnatally, and it is also important during preterm human birth. Considering that the developing kidney is vulnerable to early-life stressors, renal programming is a key element in the developmental programming of hypertension and renal disease. The purpose of this review is to highlight the great number of studies, most of them performed in animal models, showing the broad range of stressors involved in hypertension and renal disease programming, with a particular focus on the stressors that occur during the early postnatal period. These stressors mainly include undernutrition or specific nutritional deficits, chronic behavioral stress, exposure to environmental chemicals, and pharmacological treatments that affect some important factors involved in renal physiology. We also discuss the common molecular mechanisms that are activated by the mentioned stressors and that promote the appearance of these adult diseases, with a brief description on some reprogramming strategies, which is a relatively new and promising field to treat or to prevent these diseases.
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Huang YH, Tain YL, Hsu CN. Maternal Supplementation of Probiotics, Prebiotics or Postbiotics to Prevent Offspring Metabolic Syndrome: The Gap between Preclinical Results and Clinical Translation. Int J Mol Sci 2022; 23:10173. [PMID: 36077575 PMCID: PMC9456151 DOI: 10.3390/ijms231710173] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/01/2022] [Accepted: 09/02/2022] [Indexed: 11/21/2022] Open
Abstract
Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.
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Affiliation(s)
- Ying-Hua Huang
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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5
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Tain YL, Hsu CN. Hypertension of Developmental Origins: Consideration of Gut Microbiome in Animal Models. Biomedicines 2022; 10:biomedicines10040875. [PMID: 35453625 PMCID: PMC9030804 DOI: 10.3390/biomedicines10040875] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/29/2022] [Accepted: 04/08/2022] [Indexed: 11/29/2022] Open
Abstract
Hypertension is the leading cause of global disease burden. Hypertension can arise from early life. Animal models are valuable for giving cogent evidence of a causal relationship between various environmental insults in early life and the hypertension of developmental origins in later life. These insults consist of maternal malnutrition, maternal medical conditions, medication use, and exposure to environmental chemicals/toxins. There is a burgeoning body of evidence on maternal insults can shift gut microbiota, resulting in adverse offspring outcomes later in life. Emerging evidence suggests that gut microbiota dysbiosis is involved in hypertension of developmental origins, while gut microbiota-targeted therapy, if applied early, is able to help prevent hypertension in later life. This review discusses the innovative use of animal models in addressing the mechanisms behind hypertension of developmental origins. We will also highlight the application of animal models to elucidate how the gut microbiota connects with other core mechanisms, and the potential of gut microbiota-targeted therapy as a novel preventive strategy to prevent hypertension of developmental origins. These animal models have certainly enhanced our understanding of hypertension of developmental origins, closing the knowledge gap between animal models and future clinical translation.
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Affiliation(s)
- You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-975-368-975; Fax: +886-7733-8009
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Perrone L, Valente M. The Emerging Role of Metabolism in Brain-Heart Axis: New Challenge for the Therapy and Prevention of Alzheimer Disease. May Thioredoxin Interacting Protein (TXNIP) Play a Role? Biomolecules 2021; 11:1652. [PMID: 34827650 PMCID: PMC8616009 DOI: 10.3390/biom11111652] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/02/2021] [Accepted: 11/06/2021] [Indexed: 12/15/2022] Open
Abstract
Alzheimer disease (AD) is the most frequent cause of dementia and up to now there is not an effective therapy to cure AD. In addition, AD onset occurs decades before the diagnosis, affecting the possibility to set up appropriate therapeutic strategies. For this reason, it is necessary to investigate the effects of risk factors, such as cardiovascular diseases, in promoting AD. AD shows not only brain dysfunction, but also alterations in peripheral tissues/organs. Indeed, it exists a reciprocal connection between brain and heart, where cardiovascular alterations participate to AD as well as AD seem to promote cardiovascular dysfunction. In addition, metabolic dysfunction promotes both cardiovascular diseases and AD. In this review, we summarize the pathways involved in the regulation of the brain-heart axis and the effect of metabolism on these pathways. We also present the studies showing the role of the gut microbiota on the brain-heart axis. Herein, we propose recent evidences of the function of Thioredoxin Interacting protein (TXNIP) in mediating the role of metabolism on the brain-heart axis. TXNIP is a key regulator of metabolism at both cellular and body level and it exerts also a pathological function in several cardiovascular diseases as well as in AD.
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Affiliation(s)
- Lorena Perrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Mariarosaria Valente
- Department of Medicine, University of Udine, 33100 Udine, Italy;
- Clinical Neurology Unit, Department of Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale, University Hospital, 33100 Udine, Italy
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7
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Guo Y, Wang B, Gao H, Gao L, Hua R, Xu JD. ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology. Front Mol Biosci 2021; 8:708336. [PMID: 34631794 PMCID: PMC8493804 DOI: 10.3389/fmolb.2021.708336] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/11/2021] [Indexed: 12/25/2022] Open
Abstract
The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.
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Affiliation(s)
- Yuexin Guo
- Department of Oral Medicine "5+3" Program, Basic Medical College, Capital Medical University, Beijing, China
| | - Boya Wang
- Undergraduate Student of 2018 Eight Program of Clinical Medicine, Peking University Health Science Center, Beijing, China
| | - Han Gao
- Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, China
| | - Lei Gao
- Department of Bioinformatics, School of Biomedical Engineering, Capital Medical University, Beijing, China
| | - Rongxuan Hua
- Department of Clinical Medicine "5+3" Program, Basic Medical College, Capital Medical University, Beijing, China
| | - Jing-Dong Xu
- Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, China
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8
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Hsu CN, Tain YL. The First Thousand Days: Kidney Health and Beyond. Healthcare (Basel) 2021; 9:1332. [PMID: 34683012 PMCID: PMC8544398 DOI: 10.3390/healthcare9101332] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 09/25/2021] [Accepted: 10/03/2021] [Indexed: 12/12/2022] Open
Abstract
The global burden of chronic kidney disease (CKD) is rising. A superior strategy to advance global kidney health is required to prevent and treat CKD early. Kidney development can be impacted during the first 1000 days of life by numerous factors, including malnutrition, maternal illness, exposure to chemicals, substance abuse, medication use, infection, and exogenous stress. In the current review, we summarize environmental risk factors reported thus far in clinical and experimental studies relating to the programming of kidney disease, and systematize the knowledge on common mechanisms underlying renal programming. The aim of this review is to discuss the primary and secondary prevention actions for enhancing kidney health from pregnancy to age 2. The final task is to address the potential interventions to target renal programming through updating animal studies. Together, we can enhance the future of global kidney health in the first 1000 days of life.
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Affiliation(s)
- Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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9
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Machado AS, Oliveira JR, de F Lelis D, D Guimarães VH, de Paula AMB, Guimarães ALS, Brandi IV, de Carvalho BMA, da Costa DV, Vieira CR, Pereira UA, de Oliveira Costa T, Andrade JMO, Dos Santos RAS, Santos SHS. Oral angiotensin-(1-7) peptide modulates intestinal microbiota improving metabolic profile in obese mice. Protein Pept Lett 2021; 28:1127-1137. [PMID: 34397321 DOI: 10.2174/0929866528666210816115645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/25/2021] [Accepted: 06/15/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Obesity is a serious health problem which dysregulate Renin-Angiotensin System and intestinal microbiota. OBJECTIVE The present study aimed to evaluate the Angiotensin-(1-7) [ANG-(1-7)] oral formulation effects on obese mice intestinal microbiota. METHODS Mice were divided into four groups: obese and non-obese treated with ANG-(1-7) and obese and non-obese without ANG-(1-7) during four weeks. RESULTS We observed a significant decrease in the fasting plasma glucose, total cholesterol, triglycerides, and Low-density lipoprotein levels and increased High-density lipoprotein in animals treated with ANG-(1-7). The histological analysis showed intestinal villi height reduction in mice treated with ANG-(1-7). Additionally, increased Bacteroidetes and decreased Firmicutes (increased Bacteroidetes/Firmicutes ratio) and Enterobacter cloacae populations were observed in the High-Fat Diet + ANG-(1-7) group. Receptor toll-like 4 (TLR4) intestinal mRNA expression was reduced in the HFD+ ANG-(1-7) group. Finally, the intestinal expression of the neutral amino acid transporter (B0AT1) was increased in animals treated with ANG-(1-7), indicating a possible mechanism associated with tryptophan uptake. CONCLUSION The results of the present study suggest for the first time an interaction between oral ANG-(1-7) and intestinal microbiota modulation.
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Affiliation(s)
- Amanda S Machado
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - Janaína R Oliveira
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - Deborah de F Lelis
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - Victor Hugo D Guimarães
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - Alfredo M B de Paula
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - André L S Guimarães
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
| | - Igor V Brandi
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Bruna Mara A de Carvalho
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Diego Vicente da Costa
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Cláudia Regina Vieira
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Ulisses Alves Pereira
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Theles de Oliveira Costa
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - João M O Andrade
- Institute of Agricultural Sciences. Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil
| | - Robson A S Dos Santos
- Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Sérgio H S Santos
- Laboratory of Health Science, Postgraduate Program in Health Sciences, Montes Claros, Minas Gerais, Brazil
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Vlasov AA, Salikova SP, Golovkin NV, Grinevich VB. Intestinal Microbial-tissue Complex and Chronic Heart Failure (part 1): Pathogenesis. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2021; 17:462-469. [DOI: 10.20996/1819-6446-2021-06-12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Antigenic and metabolic integration of the intestinal microbiota into the homeostasis of the human body is a factor that claims to play a key role in the pathogenesis of cardiovascular diseases. It acquires special significance against the background of the decrease in blood circulation and congestion in the digestive system during chronic heart failure. Aim of the review is analysis and synthesis of studies results on the role of intestinal microbiocenosis in the pathogenesis of heart remodeling and chronic heart failure. The search for articles was conducted in databases eLIBRARY.RU and Medline for the key terms "gut microbiota (microbiome, microbiocenosis)", "dysbiosis (dysbacteriosis)", "excessive bacterial growth syndrome", "lipopolysaccharide (endotoxin)", "trimethylamine-N-oxide" in combination with the terms "heart failure", "myocardial remodeling", "myocardium" in Russian and English, respectively. We selected articles containing the results of clinical and experimental studies published from 1995 to 2020. Review articles were considered only on the subject of the cited original publications. Most researchers have established the relationship between chronic heart failure and dysfunction and changes in the qualitative and quantitative composition of intestinal microbiocenosis. As negative changes, it is customary to note the proliferation of gram-negative opportunistic bacteria with concomitant endotoxinemia and a decrease in the pool of commensal microbiota. The available data suggest that the participation of the intestinal microbial-tissue complex in the pathogenesis of chronic heart failure and heart remodeling is realized through the activation of a local and then systemic inflammatory response, accompanied by cardiodepressive action of pro-inflammatory cytokines and universal proliferation factors, an imbalance of matrix metalloproteinases and their inhibitors, the initiation of apoptosis, fibrosis, and loss of contractile myocardium. Besides, a decrease in the production of short-chain and polyunsaturated fatty acids and vitamins by the commensal microbiota may be associated with changes in the electrical properties of cardiomyocyte membranes, a decrease in the systolic function of the left ventricle of the heart, and an increase in the risk of sudden cardiac death. It's also shown that the direct cardiotoxic effect of microbial molecules (lipopolysaccharides, peptidoglycans, trimethylamine-N-oxide, etc.), which interact with the receptors of cardiomyocytes and microenvironment cells, can cause the development of myocardial remodeling and its dysfunction. Recent studies have established mechanisms of myocardial remodeling mediated by microbial molecules, which may be associated with new strategies for the treatment and prevention of heart failure.
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11
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Fang LG, Zhou Q. Remarkable gastrointestinal and liver manifestations of COVID-19: A clinical and radiologic overview. World J Clin Cases 2021; 9:4969-4979. [PMID: 34307547 PMCID: PMC8283617 DOI: 10.12998/wjcc.v9.i19.4969] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 03/13/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) raging around the world still has not been effectively controlled in most countries and regions. As a severe acute respiratory syndrome coronavirus, in addition to the most common infectious pneumonia, it can also cause digestive system disease such as diarrhea, nausea, vomiting, liver function damage, etc. In medical imaging, it manifests as thickening of the intestinal wall, intestinal perforation, pneumoperitoneum, ascites and decreased liver density. Angiotensin-converting enzyme 2 has great significance in COVID-19-related digestive tract diseases. In this review, we summarized the data on the clinical and imaging manifestations of gastrointestinal and liver injury caused by COVID-19 so far and explored its possible pathogenesis.
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Affiliation(s)
- Li-Guang Fang
- Department of Medical Imaging, Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, Guangdong Province, China
| | - Quan Zhou
- Department of Medical Imaging, Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, Guangdong Province, China
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12
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Cardiovascular Diseases of Developmental Origins: Preventive Aspects of Gut Microbiota-Targeted Therapy. Nutrients 2021; 13:nu13072290. [PMID: 34371800 PMCID: PMC8308390 DOI: 10.3390/nu13072290] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/24/2021] [Accepted: 06/30/2021] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.
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13
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Zhu C, He G, Yin Q, Zeng L, Ye X, Shi Y, Xu W. Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge. J Med Virol 2021; 93:5729-5741. [PMID: 34125455 PMCID: PMC8427004 DOI: 10.1002/jmv.27132] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 06/03/2021] [Indexed: 12/15/2022]
Abstract
The global coronavirus disease 2019 (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS‐CoV‐2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID‐19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS‐CoV‐2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS‐CoV‐2 S protein as well as recent updates on the cell entry mechanism of the SARS‐CoV‐2, paving the way for exploring more structure‐guided strategies against SARS‐CoV‐2.
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Affiliation(s)
- Chaogeng Zhu
- Translational Medicine Laboratory of Pancreatic Diseases, Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Guiyun He
- Department of Ophthalmology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Qinqin Yin
- Department of Ophthalmology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Lin Zeng
- Institute of Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Xiangli Ye
- Department of Medical Laboratory Science, School of Medicine, Hunan Normal University, Changsha, China
| | - Yongzhong Shi
- Institute of Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Wei Xu
- Institute of Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
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14
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Maternal resveratrol therapy protected adult rat offspring against hypertension programmed by combined exposures to asymmetric dimethylarginine and trimethylamine-N-oxide. J Nutr Biochem 2021; 93:108630. [PMID: 33798707 DOI: 10.1016/j.jnutbio.2021.108630] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 01/10/2021] [Accepted: 03/10/2021] [Indexed: 12/19/2022]
Abstract
Resveratrol, a phytochemical, has shown antioxidant properties and potential benefits in hypertension. Asymmetric dimethylarginine (ADMA)-related nitric oxide deficiency and gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) have been linked to hypertension. We aimed to test whether maternal resveratrol therapy would protect adult offspring against hypertension programmed by prenatal exposure to ADMA and TMAO. Pregnant Sprague-Dawley rats received ADMA 10 mg/kg/day (A), TMAO 0.65 mg/hr (T), ADMA+TMAO (AT), or vesicle (CV). One group of ADMA+TMAO-exposed rats received 50 mg/L of resveratrol in drinking water during pregnancy and lactation periods (ATR). Male offspring (n = 8/group) were assigned to five groups: CV, A, T, AT, and ATR. Rats were killed at 12 weeks of age. ADMA exposure caused the elevation of blood pressure in 12-week-old male offspring, which was exacerbated by TMAO exposure. Treatment with resveratrol rescued hypertension programmed by combined ADMA and TMAO exposure. This was accompanied by alterations in the compositions of gut microbiota and increased fecal butyrate levels. Both the abundance of the butyrate-producing genera Lachnospiraceae and Ruminococcaceae were augmented by resveratrol. Meanwhile, resveratrol therapy significantly increased the abundance of the Cyanobiaceae and Erysipelotrichaceae families. Moreover, the protective effects of resveratrol were related to the mediation of the renin-angiotensin system . Our data provide new insights into the protective mechanisms of resveratrol against hypertension programmed by ADMA and TMAO, including regulation of gut microbiota and their metabolites, the renin-angiotensin system, and nitric oxide pathway. Resveratrol might be a potential reprogramming strategy to protect against the hypertension of developmental origins.
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15
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Han KY, Qiao Q, Zhu YQ, Chen XG, Kang XX, Zhang GF, Cai XC, Du Y, Jin J, Di RM, Yang CX, Zhang FX, Xu YJ. Atrial Arrhythmias in Patients with Severe COVID-19. Cardiol Res Pract 2021; 2021:8874450. [PMID: 33777449 PMCID: PMC7955658 DOI: 10.1155/2021/8874450] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 02/21/2021] [Accepted: 03/02/2021] [Indexed: 12/15/2022] Open
Abstract
The number of confirmed COVID-19 cases has increased drastically; however, information regarding the impact of this disease on the occurrence of arrhythmias is scarce. The aim of this study was to determine the impact of COVID-19 on arrhythmia occurrence. This prospective study included patients with COVID-19 treated at the Leishenshan Temporary Hospital of Wuhan City, China, from February 24 to April 5, 2020. Demographic, comorbidity, and arrhythmias data were collected from patients with COVID-19 (n = 84) and compared with control data from patients with bacterial pneumonia (n = 84) infection. Furthermore, comparisons were made between patients with severe and nonsevere COVID-19 and between older and younger patients. Compared with patients with bacterial pneumonia, those with COVID-19 had higher total, mean, and minimum heart rates (all P < 0.01). Patients with severe COVID-19 (severe and critical type diseases) developed more atrial arrhythmias compared with those with nonsevere symptoms. Plasma creatine kinase isoenzyme (CKMB) levels (P=0.01) were higher in the severe group than in the nonsevere group, and there were more deaths in the severe group than in the nonsevere group (6 (15%) vs. 3 (2.30%); P=0.05). Premature atrial contractions (PAC) and nonsustained atrial tachycardia (NSAT) were significantly positively correlated with plasma CKMB levels but not with high-sensitive cardiac troponin I or myoglobin levels. Our data demonstrate that COVID-19 patients have higher total, mean, and minimum heart rates compared with those with bacterial pneumonia. Patients with severe or critical disease had more frequent atrial arrhythmias (including PAC and AF) and higher CKMB levels and mortality than those with nonsevere symptoms.
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Affiliation(s)
- Kai-Yue Han
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
- Leishenshan Temporary Hospital, Wuhan, China
| | - Qi Qiao
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Ye-Qian Zhu
- Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xin-Guang Chen
- Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xing-Xing Kang
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Gao-Feng Zhang
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
- Leishenshan Temporary Hospital, Wuhan, China
| | - Xun-Chao Cai
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China
| | - Yong Du
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
- Leishenshan Temporary Hospital, Wuhan, China
| | - Jing Jin
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
- Leishenshan Temporary Hospital, Wuhan, China
| | - Ruo-Min Di
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Chen-Xi Yang
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Feng-Xiang Zhang
- Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Ying-Jia Xu
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
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16
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Hsu CN, Tain YL. Targeting the Renin-Angiotensin-Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins. Int J Mol Sci 2021; 22:ijms22052298. [PMID: 33669059 PMCID: PMC7956566 DOI: 10.3390/ijms22052298] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 02/21/2021] [Accepted: 02/23/2021] [Indexed: 02/07/2023] Open
Abstract
The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.
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Affiliation(s)
- Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Correspondence: ; Tel.: +886-975-056-995; Fax: +886-7733-8009
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17
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Bian J, Li Z. Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator. Acta Pharm Sin B 2021; 11:1-12. [PMID: 33072500 PMCID: PMC7553008 DOI: 10.1016/j.apsb.2020.10.006] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/29/2020] [Accepted: 09/07/2020] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.
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Affiliation(s)
- Jingwei Bian
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
| | - Zijian Li
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
- Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
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18
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Bakkar NMZ, Dwaib HS, Fares S, Eid AH, Al-Dhaheri Y, El-Yazbi AF. Cardiac Autonomic Neuropathy: A Progressive Consequence of Chronic Low-Grade Inflammation in Type 2 Diabetes and Related Metabolic Disorders. Int J Mol Sci 2020; 21:9005. [PMID: 33260799 PMCID: PMC7730941 DOI: 10.3390/ijms21239005] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 12/11/2022] Open
Abstract
Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality. Recent research relates the pathogenesis of cardiovascular disease in T2D to an ensuing chronic, low-grade proinflammatory and pro-oxidative environment, being the hallmark of the metabolic syndrome. Metabolic inflammation emerges as adipose tissue inflammatory changes extending systemically, on the advent of hyperglycemia, to reach central regions of the brain. In light of changes in glucose and insulin homeostasis, dysbiosis or alteration of the gut microbiome (GM) emerges, further contributing to inflammatory processes through increased gut and blood-brain barrier permeability. Interestingly, studies reveal that the determinants of oxidative stress and inflammation progression exist at the crossroad of CAN manifestations, dictating their evolution along the natural course of T2D development. Indeed, sympathetic and parasympathetic deterioration was shown to correlate with markers of adipose, vascular, and systemic inflammation. Additionally, evidence points out that dysbiosis could promote a sympatho-excitatory state through differentially affecting the secretion of hormones and neuromodulators, such as norepinephrine, serotonin, and γ-aminobutyric acid, and acting along the renin-angiotensin-aldosterone axis. Emerging neuronal inflammation and concomitant autophagic defects in brainstem nuclei were described as possible underlying mechanisms of CAN in experimental models of metabolic syndrome and T2D. Drugs with anti-inflammatory characteristics provide potential avenues for targeting pathways involved in CAN initiation and progression. The aim of this review is to delineate the etiology of CAN in the context of a metabolic disorder characterized by elevated oxidative and inflammatory load.
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Affiliation(s)
- Nour-Mounira Z. Bakkar
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Riad El-Solh 1107 2020, Beirut 11-0236, Lebanon; (N.-M.Z.B.); (H.S.D.); (A.H.E.)
| | - Haneen S. Dwaib
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Riad El-Solh 1107 2020, Beirut 11-0236, Lebanon; (N.-M.Z.B.); (H.S.D.); (A.H.E.)
| | - Souha Fares
- Rafic Hariri School of Nursing, American University of Beirut, Riad El-Solh 1107 2020, Beirut 11-0236, Lebanon;
| | - Ali H. Eid
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Riad El-Solh 1107 2020, Beirut 11-0236, Lebanon; (N.-M.Z.B.); (H.S.D.); (A.H.E.)
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha 2713, Qatar
| | - Yusra Al-Dhaheri
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, UAE
| | - Ahmed F. El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Riad El-Solh 1107 2020, Beirut 11-0236, Lebanon; (N.-M.Z.B.); (H.S.D.); (A.H.E.)
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
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19
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de Oliveira AP, Lopes ALF, Pacheco G, de Sá Guimarães Nolêto IR, Nicolau LAD, Medeiros JVR. Premises among SARS-CoV-2, dysbiosis and diarrhea: Walking through the ACE2/mTOR/autophagy route. Med Hypotheses 2020; 144:110243. [PMID: 33254549 PMCID: PMC7467124 DOI: 10.1016/j.mehy.2020.110243] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/30/2020] [Accepted: 08/30/2020] [Indexed: 12/22/2022]
Abstract
Recently, a new coronavirus (SARS-CoV-2) was discovered in China. Due to its high level of contagion, it has already reached most countries, quickly becoming a pandemic. Although the most common symptoms are related to breathing problems, SARS-CoV-2 infections also affect the gastrointestinal tract culminating in inflammation and diarrhea. However, the mechanisms related to these enteric manifestations are still not well understood. Evidence shows that the SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) in host cells as a viral invasion mechanism and can infect the lungs and the gut. Other viruses have already been linked to intestinal symptoms through binding to ACE2. In turn, this medical hypothesis article conjectures that the ACE2 downregulation caused by the SARS-CoV-2 internalization could lead to decreased activation of the mechanistic target of mTOR with increased autophagy and lead to intestinal dysbiosis, resulting in diarrhea. Besides that, dysbiosis can directly affect the respiratory system through the lungs. Although there are clues to other viruses that modulate the ACE2/gut/lungs axis, including the participation of autophagy and dysbiosis in the development of gastrointestinal symptoms, there is still no evidence of the ACE2/mTOR/autophagy pathway in SARS-CoV-2 infections. Thus, we propose that the new coronavirus causes a change in the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway into enterocytes. Our assumption is supported by premises that unregulated intestinal microbiota increases the susceptibility to other diseases and extra-intestinal manifestations, which can even cause remote damage in lungs. These putative connections lead us to suggest and encourage future studies aiming at assessing the aforementioned hypothesis and regulating dysbiosis caused by SARS-CoV-2 infection, in order to confirm the decrease in lung injuries and the improvement in the prognosis of the disease.
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Affiliation(s)
| | - André Luis Fernandes Lopes
- Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of the Parnaíba Delta, Parnaíba, Piauí, Brazil
| | - Gabriella Pacheco
- Medicinal Plant Research Center, NPPM, Post-graduation Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil
| | | | - Lucas Antonio Duarte Nicolau
- Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of the Parnaíba Delta, Parnaíba, Piauí, Brazil
| | - Jand Venes Rolim Medeiros
- The Northest Biotechnology Network, Federal University of Piauí, Teresina, Piauí, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of the Parnaíba Delta, Parnaíba, Piauí, Brazil; Medicinal Plant Research Center, NPPM, Post-graduation Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil.
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20
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Li M, Chen S, Xiang X, Wang Q, Liu X. Effects of SARS-CoV-2 and its functional receptor ACE2 on the cardiovascular system. Herz 2020; 45:659-662. [PMID: 33025029 PMCID: PMC7537586 DOI: 10.1007/s00059-020-04989-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 08/28/2020] [Accepted: 09/08/2020] [Indexed: 12/22/2022]
Abstract
The clinical manifestations of COVID-19 are mainly respiratory symptoms, but some patients present with cardiovascular system disease such as palpitations and shortness of breath as the first or secondary symptoms. In this paper, we describe the characteristics of SARS-CoV‑2 and its functional receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, we explore the impact of virus-induced myocardial damage, decreased ACE2 activity, immune imbalance, hypoxemia, and heart damage caused by antiviral drugs.
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Affiliation(s)
- Mingzhe Li
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065 Wuhan, China
| | - Siyang Chen
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065 Wuhan, China
| | - Xiaochen Xiang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065 Wuhan, China
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065 Wuhan, China
| | - Xiaoliu Liu
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065 Wuhan, China
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21
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Immunomodulatory effects of collagen hydrolysates from yak (Bos grunniens) bone on cyclophosphamide-induced immunosuppression in BALB/c mice. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.103420] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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