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Wen T, Chen W, Wang F, Zhang R, Chen C, Zhang M, Ma T. The roles and functions of ergothioneine in metabolic diseases. J Nutr Biochem 2025; 141:109895. [PMID: 40058711 DOI: 10.1016/j.jnutbio.2025.109895] [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: 10/18/2024] [Revised: 01/25/2025] [Accepted: 03/04/2025] [Indexed: 04/04/2025]
Abstract
The global prevalence of metabolic diseases is on the increase, and it has become a significant threat to the health and lives of individuals. Ergothioneine (EGT) is a natural betaine amino acid found in various foods, particularly mushrooms. EGT cannot be synthesized by mammals; it is absorbed into small intestinal epithelial cells by a cationic protein, the novel organic cation transporter 1 (OCTN1), and transported to certain organs including liver, spleen, kidney, lung, heart, eyes and brain. EGT has been reported to exhibit antioxidant, anti-inflammatory, anti-apoptotic, anti-aging, and metal-chelating effects. The unique chemical properties and biological functions of EGT position it as a promising candidate for the research and treatment of metabolic diseases. This review summarizes EGT's capacities, potential therapeutic effects on multiple metabolic diseases, and their specific mechanisms. Finally, we outline challenges for future research on EGT and aspire to establish it as a prospective therapeutic agent for metabolic diseases.
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Affiliation(s)
- Tingting Wen
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Wanjing Chen
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Fengjing Wang
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Rui Zhang
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
| | - Cheng Chen
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
| | - Mingliang Zhang
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
| | - Teng Ma
- Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
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Chen Y, Lai F, Xu H, He Y. Chinese herb pairs for cardiovascular and cerebrovascular diseases: Compatibility effects, pharmacological potential, clinical efficacy, and molecular mechanisms. JOURNAL OF ETHNOPHARMACOLOGY 2025; 347:119516. [PMID: 39978448 DOI: 10.1016/j.jep.2025.119516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 12/27/2024] [Accepted: 02/16/2025] [Indexed: 02/22/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cerebrovascular and cardiovascular diseases are pathophysiologically interconnected. In the past, researchers have mainly focused on developing one herbal medicine treatment. Single herb often fails to address the multifactorial pathology of these diseases. The pathogenesis and progression of the disease are complex, making the therapeutic effect of a single herb potentially limiting. Traditional Chinese medicine emphasizes herb pairs, which enhance therapeutic efficacy through synergistic interactions. AIM OF THE REVIEW This review focused on the mechanisms and potential clinical applications of Chinese herb pairs such as Astragali Radix-Carthami Flos, Salviae Miltiorrhizae Radix-Puerariae Lobatae Radix, Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix-Notoginseng Radix, Salviae Miltiorrhizae Radix-Carthami Flos, Astragali Radix-Angelicae Sinensis Radix, Notoginseng Radix-Carthami Flos, and Astragali Radix-Salviae Miltiorrhizae Radix, as well as provided a scientific basis for clinical applications of Chinese herb pairs. MATERIALS AND METHODS A systematic search and collection of studies on Chinese herb pairs in cardiovascular and cerebrovascular diseases was carried out using electronic databases such as PubMed, CNKI, Wan Fang Database, Baidu Scholar, and Web of Science. The keywords searched included Chinese herb pairs, cardiovascular disease, cerebrovascular disease, Astragali Radix, Salviae Miltiorrhizae Radix, Angelicae Sinensis Radix, Carthami Flos, Notoginseng Radix, and so on. RESULTS Studies revealed that the Chinese herb pairs had more beneficial effects than single herb and demonstrated a variety of roles in cardiovascular and cerebrovascular diseases. Preclinical studies indicated that Chinese herb pairs are more effective than single herb in treating cardiovascular and cerebrovascular diseases by modulating disease-related pathways and molecular targets. Further research is needed to fully explore their potential. The review also outlined the potential clinical applications of these Chinese herb pairs, highlighting their safety and efficacy. CONCLUSIONS Chinese herb pairs showed good promise as an alternative therapy for cardiovascular and cerebrovascular diseases due to their multi-component and multi-target characteristics. Consequently, further research was necessary to fully explore the potential of Chinese herb pairs in treating cardiovascular and cerebrovascular diseases, based on the current data.
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Affiliation(s)
- Yajie Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
| | - Feifan Lai
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang Key Laboratory of Chinese Medicine for Cardiovascular and Cerebrovascular Disease, China.
| | - Huaping Xu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang Key Laboratory of Chinese Medicine for Cardiovascular and Cerebrovascular Disease, China.
| | - Yu He
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang Key Laboratory of Chinese Medicine for Cardiovascular and Cerebrovascular Disease, China.
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Fang Z, Chang S, Niu P, Wang C, Zhang J. Multidimensional-based exploration of gut microbial and metabolite differences in patients with recurrent stroke. Neuroscience 2025; 572:35-48. [PMID: 39914520 DOI: 10.1016/j.neuroscience.2025.02.004] [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: 07/11/2024] [Revised: 01/17/2025] [Accepted: 02/02/2025] [Indexed: 03/11/2025]
Abstract
This study aims to explore the differences in gut microbes and their metabolites between patients with original and recurrent stroke, providing insights and justification for the diagnosis and prevention of ischemic stroke progression from the perspective of the gut microbiota-metabolite-brain axis. In this study, fecal samples were collected from patients with Original stroke (Os) and patients with Recurrent stroke (Rs) to assess differences in gut microbiota and to screen for different metabolites that reveal the physiological changes related to the recurrent of ischemic stroke. The results found that there was no significant change in Alpha diversity between the two groups. Beta diversity analysis revealed slight changes in community composition between two groups (Bray-Curtis), although their overall microbial abundance may not have changed (UniFrac). Compared with Os patients, Prevotella, Lachnospiraceae_UCG-010, Holdemanella, and Coprococcus were significantly depleted in the Rs group. Correlation analysis showed that the risk of stroke recurrence was negatively correlated with Lachnospiraceae_UCG-010. In Rs group, metabolites such as carbohydrates and terpene lactones were up-regulated, while those of sesquiterpenoids, triterpenoids, and fatty acids and their couplings were down-regulated. These metabolites are significantly enriched in the pathways of arachidonic acid metabolism, betaine biosynthesis, and linoleic acid metabolism. Compared with the Os, Rs was mainly characterized by minor destruction of anaerobic bacteria and significant depletion of SCFAs-producing bacteria. In addition, the related compounds involved in arachidonic acid metabolism and linoleic acid metabolism pathway may be associated with the progression of ischemic stroke.
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Affiliation(s)
- Zongwei Fang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Sijie Chang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Peiguang Niu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Chunhua Wang
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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Kim HK, Park S, Kim SW, Park ES, Hong JY, Hong I, Baek MS. Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea. J Prev Alzheimers Dis 2025; 12:100059. [PMID: 40155153 DOI: 10.1016/j.tjpad.2025.100059] [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: 10/22/2024] [Revised: 12/19/2024] [Accepted: 01/02/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Alzheimer's disease and vascular dementia are two of the most common causes of dementia. While early diagnosis and intervention are crucial, available treatments and research concerning the mild cognitive impairment stage remain limited. This study aimed to evaluate the real-world effectiveness and safety of L-α glycerylphosphorylcholine in this context. OBJECTIVES To investigate the impact of L-α glycerylphosphorylcholine on the risk of conversion from mild cognitive impairment to Alzheimer's disease dementia and vascular dementia, as well as its influence on stroke risk DESIGN: A nationwide, population-based cohort study SETTING: Data from South Korea's National Health Insurance Service PARTICIPANTS: Overall, 508,107 patients newly diagnosed with mild cognitive impairment between 2013 and 2016 were included. INTERVENTION Patients were classified as users or non-users of L-α glycerylphosphorylcholine based on prescription records. MEASUREMENTS The primary outcomes were the risk of progression to Alzheimer's disease dementia and vascular dementia. Stroke risk was examined as a secondary outcome. A time-dependent Cox regression analysis was used to adjust for demographic and clinical factors. RESULTS Compared to non-users, L-α glycerylphosphorylcholine users had a lower risk of progression to Alzheimer's disease dementia (hazard ratio = 0.899, 95 % confidence interval: 0.882-0.918) and vascular dementia (hazard ratio = 0.832, 95 % confidence interval: 0.801-0.865) within 2,435,924 and 662,281.6 person-years, respectively. In patients under 65, L-α glycerylphosphorylcholine significantly reduced the risk of progression to Alzheimer's and vascular dementia. Stroke risk significantly decreased in patients who did not progress to dementia but not in those who did. CONCLUSIONS L-α Glycerylphosphorylcholine reduces dementia conversion and stroke risk in patients with mild cognitive impairment, making it a viable early intervention. Future large-scale randomized controlled studies should examine its effects on other dementia subtypes and long-term cognitive outcomes.
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Affiliation(s)
- Han-Kyeol Kim
- Department of Neurology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Sojeong Park
- Department of Biostatistics and Computing, Graduate School, Yonsei University, Seoul, South Korea
| | - Sung-Woo Kim
- Department of Neurology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea; Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Eun Seok Park
- Department of Neurology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jin Yong Hong
- Department of Neurology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Ickpyo Hong
- Department of Occupational Therapy, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju, South Korea
| | - Min Seok Baek
- Department of Neurology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea; Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, South Korea.
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Chen L, Wang X, Wang S, Liu W, Song Z, Liao H. The impact of gut microbiota on the occurrence, treatment, and prognosis of ischemic stroke. Neurobiol Dis 2025; 207:106836. [PMID: 39952411 DOI: 10.1016/j.nbd.2025.106836] [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: 12/30/2024] [Revised: 02/05/2025] [Accepted: 02/08/2025] [Indexed: 02/17/2025] Open
Abstract
Ischemic stroke (IS) is a cerebrovascular disease that predominantly affects middle-aged and elderly populations, exhibiting high mortality and disability rates. At present, the incidence of IS is increasing annually, with a notable trend towards younger affected individuals. Recent discoveries concerning the "gut-brain axis" have established a connection between the gut and the brain. Numerous studies have revealed that intestinal microbes play a crucial role in the onset, progression, and outcomes of IS. They are involved in the entire pathophysiological process of IS through mechanisms such as chronic inflammation, neural regulation, and metabolic processes. Although numerous studies have explored the relationship between IS and intestinal microbiota, comprehensive analyses of specific microbiota is relatively scarce. Therefore, this paper provides an overview of the typical changes in gut microbiota following IS and investigates the role of specific microorganisms in this context. Additionally, it presents a comprehensive analysis of post-stroke microbiological therapy and the relationship between IS and diet. The aim is to identify potential microbial targets for therapeutic intervention, as well as to highlight the benefits of microbiological therapies and the significance of dietary management. Overall, this paper seeks to provide key strategies for the treatment and management of IS, advocating for healthy diets and health programs for individuals. Meanwhile, it may offer a new perspective on the future interdisciplinary development of neurology, microbiology and nutrition.
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Affiliation(s)
- Liying Chen
- Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Xi Wang
- Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Shiqi Wang
- Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | - Weili Liu
- Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
| | | | - Huiling Liao
- Neurology Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
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Gureev AP, Nesterova VV, Babenkova PI, Ivanov ME, Plotnikov EY, Silachev DN. L-Carnitine and Mildronate Demonstrate Divergent Protective Effects on Mitochondrial DNA Quality Control and Inflammation Following Traumatic Brain Injury. Int J Mol Sci 2025; 26:2902. [PMID: 40243464 PMCID: PMC11988827 DOI: 10.3390/ijms26072902] [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: 02/17/2025] [Revised: 03/19/2025] [Accepted: 03/19/2025] [Indexed: 04/18/2025] Open
Abstract
Traumatic brain injuries (TBIs) are a serious problem affecting individuals of all ages. Mitochondrial dysfunctions represent a significant form of secondary injury and may serve as a promising target for therapeutic intervention. Our research demonstrated that craniotomy, which precedes the experimental induction of trauma in mice, can cause considerable damage to mitochondrial DNA (mtDNA), disrupt the regulatory expression of angiogenesis, and increase inflammation. However, the reduction in the mtDNA copy number and glial activation occur only after a direct impact to the brain. We explored two potential therapeutic agents: the dietary supplement L-carnitine-a potential reserve source of ATP for the brain-and the cardiac drug mildronate, which inhibits L-carnitine but activates alternative compensatory pathways for the brain to adapt to metabolic disturbances. We found that L-carnitine injections could protect against mtDNA depletion by promoting mitochondrial biogenesis. However, they also appeared to aggravate inflammatory responses, likely due to changes in the composition of the gut microbiome. On the other hand, mildronate enhanced the expression of genes related to angiogenesis while also reducing local and systemic inflammation. Therefore, both compounds, despite their opposing metabolic effects, have the potential to be used in the treatment of secondary injuries caused by TBI.
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Affiliation(s)
- Artem P. Gureev
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia; (A.P.G.); (V.V.N.); (P.I.B.)
| | - Veronika V. Nesterova
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia; (A.P.G.); (V.V.N.); (P.I.B.)
| | - Polina I. Babenkova
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia; (A.P.G.); (V.V.N.); (P.I.B.)
| | - Mikhail E. Ivanov
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; (M.E.I.); (E.Y.P.)
| | - Egor Y. Plotnikov
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; (M.E.I.); (E.Y.P.)
| | - Denis N. Silachev
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; (M.E.I.); (E.Y.P.)
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Jiang J, Xie H, Cao S, Xu X, Zhou J, Liu Q, Ding C, Liu M. Post-stroke depression: exploring gut microbiota-mediated barrier dysfunction through immune regulation. Front Immunol 2025; 16:1547365. [PMID: 40098959 PMCID: PMC11911333 DOI: 10.3389/fimmu.2025.1547365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 02/17/2025] [Indexed: 03/19/2025] Open
Abstract
Post-stroke depression (PSD) is one of the most common and devastating neuropsychiatric complications in stroke patients, affecting more than one-third of survivors of ischemic stroke (IS). Despite its high incidence, PSD is often overlooked or undertreated in clinical practice, and effective preventive measures and therapeutic interventions remain limited. Although the exact mechanisms of PSD are not fully understood, emerging evidence suggests that the gut microbiota plays a key role in regulating gut-brain communication. This has sparked great interest in the relationship between the microbiota-gut-brain axis (MGBA) and PSD, especially in the context of cerebral ischemia. In addition to the gut microbiota, another important factor is the gut barrier, which acts as a frontline sensor distinguishing between beneficial and harmful microbes, regulating inflammatory responses and immunomodulation. Based on this, this paper proposes a new approach, the microbiota-immune-barrier axis, which is not only closely related to the pathophysiology of IS but may also play a critical role in the occurrence and progression of PSD. This review aims to systematically analyze how the gut microbiota affects the integrity and function of the barrier after IS through inflammatory responses and immunomodulation, leading to the production or exacerbation of depressive symptoms in the context of cerebral ischemia. In addition, we will explore existing technologies that can assess the MGBA and potential therapeutic strategies for PSD, with the hope of providing new insights for future research and clinical interventions.
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Affiliation(s)
- Jia Jiang
- The Second Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, China
| | - Haihua Xie
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
| | - Sihui Cao
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
| | - Xuan Xu
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
| | - Jingying Zhou
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
| | - Qianyan Liu
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
| | - Changsong Ding
- School of Information Science and Engineering, Hunan University of Chinese Medicine, Changsha, China
| | - Mi Liu
- School of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China
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Zhu S, He Y, Lei JN, Liu YF, Xu YJ. The chemical and biological characteristics of fatty acid esters of hydroxyl fatty acids. Nutr Rev 2025; 83:e427-e442. [PMID: 38412339 DOI: 10.1093/nutrit/nuae005] [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] [Indexed: 02/29/2024] Open
Abstract
With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods.
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Affiliation(s)
- Shuang Zhu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Yuan He
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Jing-Nan Lei
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Yuan-Fa Liu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Yong-Jiang Xu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu, People's Republic of China
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Li X, Liu S, Wang F, Li X, Liu H, Lian T, Yan X, Yang L, Wei J, Li Y, Cai T. Dietary herbs that interact with gut microbiota: roles as anti-stroke agents. Food Sci Biotechnol 2025; 34:547-562. [PMID: 39958164 PMCID: PMC11822190 DOI: 10.1007/s10068-024-01698-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 08/08/2024] [Accepted: 08/12/2024] [Indexed: 02/18/2025] Open
Abstract
Growing evidence suggests that dietary herbs can prevent stroke by regulating the composition and structure of gut microbiota. The components of dietary herbs can also be metabolized or converted into bioactive molecules for treating stroke by gut microbiota, and exert therapeutic effects by inhibiting inflammation, oxidative stress, apoptosis, and other processes caused by stroke. A deep understanding of the mechanism of gut microbiota-mediated dietary herbal intervention in stroke is of great significance for the treatment and drug screening of stroke diseases. In this review, we summarise the complex bidirectional relationship between stroke and gut microbiota and provide a detailed introduction to the mechanism of the interaction between dietary herbs and gut microbiota in intervening in stroke. In addition, we also discuss the limitations of current research and potential directions in this field, hoping to provide ideas and references for the treatment and drug development of stroke diseases. Graphical abstract Dietary herbs and active ingredients can balance the intestinal microbiota disorders in stroke patients or models, and herbal ingredients can be converted into more easily absorbed active substances under the action of microorganisms, thereby exerting therapeutic effect on stroke diseases.
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Affiliation(s)
- Xia Li
- Ningbo No. 2 Hospital, Ningbo, 315099 China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315000 China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Sijia Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Fang Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Xinyue Li
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
- Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Huiru Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Tingting Lian
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Xingxu Yan
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Liu Yang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Jinxia Wei
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Yubo Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Ting Cai
- Ningbo No. 2 Hospital, Ningbo, 315099 China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315000 China
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10
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He X, Yuan X, Shu Q, Gao Y, Chen Y, Liu Y, Xu J, Zhang Y, Cao G. Therapeutic effects of traditional Chinese medicine Hua-Feng-Dan in a rat model of ischemic stroke involve renormalization of gut microbiota. Front Pharmacol 2025; 16:1485340. [PMID: 39931688 PMCID: PMC11808003 DOI: 10.3389/fphar.2025.1485340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025] Open
Abstract
Hua-Feng-Dan is a traditional Chinese medicine used to treat ischemic stroke, but little is known about its therapeutic mechanism. This study explored whether and how the mechanism involves readjustment of gut microbiota. Rats were subjected to middle cerebral artery occlusion as a model of ischemic stroke or to sham surgery, then treated or not with Hua-Feng-Dan. The different groups of animals were compared in terms of neurological score, cerebral infarct volume, brain edema, brain and gut histopathology to assess stroke severity. They were also compared in terms of indices of intestinal barrier permeability, inflammation and oxidative stress, brain metabolites as well as composition of the gut microbiota and their metabolites. Hua-Feng-Dan significantly reduced cerebral infarct volume and brain water content and improved neurological score, ischemic brain histopathology, and gut histopathology. It partially reversed stroke-induced intestinal barrier disruption and leakage, inflammation, dyslipidemia and oxidative stress, as well as the stroke-induced increase in pathogenic gut microbiota (e.g., Escherichia-Shigella, Enterococcus, Clostridium_innocuum_group) and decrease in beneficial microbiota (e.g., Lachnospiraceae, unclassified__f__Lachnospiracea and Ruminococcus_torques_group). The treatment altered levels of 39 and 38 metabolites produced during gut microbial and brain tissue metabolism respectively, mainly of amino acids, nucleosides, short-chain fatty acids, and essential fatty acids. Levels of factors related to inflammation and intestinal barrier permeability correlated positively with relative abundance of Escherichia-Shigella and Clostridium_innocuum_group, and negatively with 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, dihomo-α-linolenic acid, dihomolinoleic acid, and 10-nitrolinoleic acid. Conversely, levels of 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, and 10-nitrolinoleic acid correlated positively with relative abundance of unclassified__f__Lachnospiracea. Our results suggest that Hua-Feng-Dan may mitigate ischemic stroke injury by renormalizing gut microbiota and restoring gut barrier function, gut metabolism, thereby helping to alleviate inflammatory, neurological damage, and brain metabolic disorders.
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Affiliation(s)
- Xiaoxia He
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Xiaofeng Yuan
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Qilin Shu
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yayang Gao
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Youli Chen
- Zunyi Liao Yuan He Tang Pharmaceutical, Zunyi, China
| | - Yao Liu
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- National Engineering Technology Research Center for Miao Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jian Xu
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- National Engineering Technology Research Center for Miao Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yongping Zhang
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- National Engineering Technology Research Center for Miao Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Guoqiong Cao
- College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- National Engineering Technology Research Center for Miao Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
- Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
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11
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Kaur M, Aran KR, Paswan R. A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective. Psychopharmacology (Berl) 2024; 241:2409-2430. [PMID: 39463207 DOI: 10.1007/s00213-024-06708-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 10/18/2024] [Indexed: 10/29/2024]
Abstract
RATIONALE Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation. OBJECTIVE The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities. RESULTS Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions. CONCLUSION In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.
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Affiliation(s)
- Manpreet Kaur
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India
| | - Khadga Raj Aran
- Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
| | - Raju Paswan
- Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, 142001, India
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Ahmadi S, Hasani A, Khabbaz A, Poortahmasbe V, Hosseini S, Yasdchi M, Mehdizadehfar E, Mousavi Z, Hasani R, Nabizadeh E, Nezhadi J. Dysbiosis and fecal microbiota transplant: Contemplating progress in health, neurodegeneration and longevity. Biogerontology 2024; 25:957-983. [PMID: 39317918 DOI: 10.1007/s10522-024-10136-4] [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: 05/21/2024] [Accepted: 08/30/2024] [Indexed: 09/26/2024]
Abstract
The gut-brain axis plays an important role in mental health. The intestinal epithelial surface is colonized by billions of commensal and transitory bacteria, known as the Gut Microbiota (GM). However, potential pathogens continuously stimulate intestinal immunity when they find the place. The last two decades have witnessed several studies revealing intestinal bacteria as a key factor in the health-disease balance of the gut, as well as disease-emergent in other parts of the body. Various neurological processes, such as cognition, learning, and memory, could be affected by dysbiosis in GM. Additionally, the aging process and longevity are related to systemic inflammation caused by dysbiosis. Commensal GM affects brain development, behavior, and healthy aging suggesting that building changes in GM might be a potential therapeutic method. The innovation in GM dysbiosis is intervention by Fecal Microbiota Transplantation (FMT), which has been confirmed as a therapy for recurrent Clostridium difficile infections and is promising for other clinical disorders, such as Parkinson's disease, Multiple Sclerosis (MS), Alzheimer's disease, and depression. Additionally, FMT may be possible to promote healthy aging, and extend longevity. This review aims to connect dysbiosis, neurological disorders, and aging and the potential of FMT as a therapeutic strategy to treat these disorders, and to enhance the quality of life in the elderly.
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Affiliation(s)
- Somayeh Ahmadi
- Infectious and Tropical Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alka Hasani
- Infectious and Tropical Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Aytak Khabbaz
- Neurosciences Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahdat Poortahmasbe
- Infectious and Tropical Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samaneh Hosseini
- Neurosciences Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Yasdchi
- Neurosciences Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Mehdizadehfar
- Neurosciences Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Mousavi
- Department of Psychology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roqaiyeh Hasani
- School of Medicine, Istanbul Okan University, Tuzla, 34959, Istanbul, Turkey
| | - Edris Nabizadeh
- Infectious and Tropical Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Nezhadi
- Infectious and Tropical Diseases Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Zhou Y, Zhang Y, Jin S, Lv J, Li M, Feng N. The gut microbiota derived metabolite trimethylamine N-oxide: Its important role in cancer and other diseases. Biomed Pharmacother 2024; 177:117031. [PMID: 38925016 DOI: 10.1016/j.biopha.2024.117031] [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: 04/26/2024] [Revised: 06/21/2024] [Accepted: 06/21/2024] [Indexed: 06/28/2024] Open
Abstract
An expanding body of research indicates a correlation between the gut microbiota and various diseases. Metabolites produced by the gut microbiota act as mediators between the gut microbiota and the host, interacting with multiple systems in the human body to regulate physiological or pathological functions. However, further investigation is still required to elucidate the underlying mechanisms. One such metabolite involved in choline metabolism by gut microbes is trimethylamine (TMA), which can traverse the intestinal epithelial barrier and enter the bloodstream, ultimately reaching the liver where it undergoes oxidation catalyzed by flavin-containing monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). While some TMAO is eliminated through renal excretion, remaining amounts circulate in the bloodstream, leading to systemic inflammation, endoplasmic reticulum (ER) stress, mitochondrial stress, and disruption of normal physiological functions in humans. As a representative microbial metabolite originating from the gut, TMAO has significant potential both as a biomarker for monitoring disease occurrence and progression and for tailoring personalized treatment strategies for patients. This review provides an extensive overview of TMAO sources and its metabolism in human blood, as well as its impact on several major human diseases. Additionally, we explore the latest research areas related to TMAO along with future directions.
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Affiliation(s)
- Yuhua Zhou
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Yuwei Zhang
- Nantong University Medical School, Nantong, China
| | - Shengkai Jin
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Jing Lv
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Menglu Li
- Department of Urology, Jiangnan University Medical Center, Wuxi, China.
| | - Ninghan Feng
- Wuxi School of Medicine, Jiangnan University, Wuxi, China; Nantong University Medical School, Nantong, China; Department of Urology, Jiangnan University Medical Center, Wuxi, China.
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14
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Wang H, Lin J, Fan S, Zhang X, Zhou T, Luo R, Zhang C, Zhang S, Yang Q, Hu R. Choline consumption reduces CVD risk via body composition modification. Sci Rep 2024; 14:16152. [PMID: 38997295 PMCID: PMC11245612 DOI: 10.1038/s41598-024-66039-4] [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: 02/28/2024] [Accepted: 06/26/2024] [Indexed: 07/14/2024] Open
Abstract
Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target.
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Affiliation(s)
- Haomiao Wang
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jinxin Lin
- Department of Cardiology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shitao Fan
- Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xuyang Zhang
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Tengyuan Zhou
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Ran Luo
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Chao Zhang
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shuixian Zhang
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Qingwu Yang
- Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
| | - Rong Hu
- Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
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Xie L, He M, Ying C, Chu H. Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk. Front Mol Neurosci 2024; 17:1400808. [PMID: 38932932 PMCID: PMC11199882 DOI: 10.3389/fnmol.2024.1400808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/28/2024] [Indexed: 06/28/2024] Open
Abstract
Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.
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Affiliation(s)
- Ling Xie
- Department of Critical Medicine, First People's Hospital of Linping District, Hangzhou, China
| | - Ming He
- Department of Critical Medicine, First People's Hospital of Linping District, Hangzhou, China
| | - Caidi Ying
- Department of Hepatobiliary and Pancreatic Surgery, The Traditional Chinese Medicine Hospital of Ningbo, Ningbo, China
| | - Haifeng Chu
- Department of Neurosurgery, The Traditional Chinese Medicine Hospital of Linping District, Hangzhou, China
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Shuai H, Wang Z, Xiao Y, Ge Y, Mao H, Gao J. Genetically supported causality between gut microbiota, immune cells, and ischemic stroke: a two-sample Mendelian randomization study. Front Microbiol 2024; 15:1402718. [PMID: 38894965 PMCID: PMC11185428 DOI: 10.3389/fmicb.2024.1402718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 05/06/2024] [Indexed: 06/21/2024] Open
Abstract
Background Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate the causal association between gut microbiota/immune cells and the likelihood of developing IS, employing a two-sample Mendelian randomization (MR) analysis. Methods Our comprehensive analysis utilized summary statistics from genome-wide association studies (GWAS) on gut microbiota, immune cells, and IS. The primary MR method employed was the inverse variance-weighted (IVW) approach. To address potential pleiotropy and identify outlier genetic variants, we incorporated the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity was assessed using Cochran's Q-test. Additionally, leave-one-out analysis was conducted to pinpoint any individual genetic variant influencing the observed causal associations. Finally, a reverse MR analysis was performed to explore the potential of reverse causation. Results Our investigation revealed four gut microbial taxa and 16 immune cells with a significant causal relationship with IS (p < 0.05). Notably, two bacterial features and five immunophenotypes were strongly associated with a lower IS risk: genus.Barnesiella.id.944 (OR: 0.907, 95% CI: 0.836-0.983, p = 0.018), genus.LachnospiraceaeNK4A136group.id.11319 (OR: 0.918, 95% CI: 0.853-0.983, p = 0.988), Activated & resting Treg % CD4++ (OR: 0.977, 95% CI: 0.956-0.998, p = 0.028). Additionally, significant associations between IS risk and two bacterial features along with eleven immunophenotypes were observed: genus.Paraprevotella.id.962 (OR: 1.106, 95% CI: 1.043-1.172, p < 0.001), genus.Streptococcus.id.1853 (OR: 1.119, 95% CI: 1.034-1.210, p = 0.005), CD127 on granulocyte (OR: 1.039, 95% CI: 1.009-1.070, p = 0.011). Our analyses did not reveal heterogeneity based on the Cochrane's Q-test (p > 0.05) nor indicate instances of horizontal pleiotropy according to MR-Egger and MR-PRESSO analyses (p > 0.05). Furthermore, the robustness of our MR results was confirmed through leave-one-out analysis. Conclusion Our study provides further evidence supporting the potential association between gut microbiota and immune cells in relation to IS, shedding light on the underlying mechanisms that may contribute to this condition. These findings lay a solid foundation for future investigations into targeted prevention strategies.
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Affiliation(s)
- Han Shuai
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
- Peking University People’s Hospital, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China
| | - Zi Wang
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Yinggang Xiao
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Yali Ge
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Hua Mao
- Peking University People’s Hospital, Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China
| | - Ju Gao
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
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Pu B, Zhu H, Wei L, Gu L, Zhang S, Jian Z, Xiong X. The Involvement of Immune Cells Between Ischemic Stroke and Gut Microbiota. Transl Stroke Res 2024; 15:498-517. [PMID: 37140808 DOI: 10.1007/s12975-023-01151-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 02/24/2023] [Accepted: 04/05/2023] [Indexed: 05/05/2023]
Abstract
Ischemic stroke, a disease with high mortality and disability rate worldwide, currently has no effective treatment. The systemic inflammation response to the ischemic stroke, followed by immunosuppression in focal neurologic deficits and other inflammatory damage, reduces the circulating immune cell counts and multiorgan infectious complications such as intestinal and gut dysfunction dysbiosis. Evidence showed that microbiota dysbiosis plays a role in neuroinflammation and peripheral immune response after stroke, changing the lymphocyte populations. Multiple immune cells, including lymphocytes, engage in complex and dynamic immune responses in all stages of stroke and may be a pivotal moderator in the bidirectional immunomodulation between ischemic stroke and gut microbiota. This review discusses the role of lymphocytes and other immune cells, the immunological processes in the bidirectional immunomodulation between gut microbiota and ischemic stroke, and its potential as a therapeutic strategy for ischemic stroke.
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Affiliation(s)
- Bei Pu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People's Republic of China
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China
| | - Hua Zhu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People's Republic of China
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China
| | - Liang Wei
- Organ Transplantation Center, Sichuan Provincial People's Hospital and School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, People's Republic of China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China
| | - Lijuan Gu
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China
| | - Shenqi Zhang
- Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People's Republic of China
| | - Zhihong Jian
- Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People's Republic of China.
| | - Xiaoxing Xiong
- Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People's Republic of China.
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
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Liu D, Tan S, Zhou Z, Gu S, Zuo H. Trimethylamine N-oxide, β-alanine, tryptophan index, and vitamin B6-related dietary patterns in association with stroke risk. Nutr Metab Cardiovasc Dis 2024; 34:1179-1188. [PMID: 38218714 DOI: 10.1016/j.numecd.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 11/17/2023] [Accepted: 12/06/2023] [Indexed: 01/15/2024]
Abstract
BACKGROUND AND AIMS The aim of this study was to examine the associations of dietary patterns derived by reduced-rank regression (RRR) model reflecting variation in novel biomarkers (trimethylamine N-oxide, β-alanine, tryptophan index, and vitamin B6) with stroke risk. METHODS AND RESULTS We performed analyses based on a community-based cohort study "the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC)". Factor loadings were calculated by RRR using 11 food groups collected via a validated food frequency questionnaire and the four response variables based on its nested case-control data (393 cases of stroke vs. 393 matched controls). Dietary pattern scores were derived by applying the factor loadings to the food groups in the entire cohort (n = 15,518). The associations of dietary pattern with the stroke risk were assessed using Cox proportional hazards models. The dietary pattern characterized with higher intakes of red meat and poultry but lower intakes of fresh vegetables, fresh fruits, and fish/seafoods were identified for further analyses. The hazard ratios (HR) for the highest vs. lowest quartile was 1.55 [95 % confidence interval (CI): 1.18-2.03, P trend = 0.001] for total stroke, 2.96 [95 % CI: 1.53-5.71, P trend <0.001] for non-ischemic stroke, after adjustment for sex, age, educational attainment, current smoking, current drinking, body mass index, total energy intake, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate. CONCLUSION Our findings highlight the importance of limited meat intake and increased intakes of fresh vegetables, fruits, and fish/seafoods in the prevention of stroke among Chinese adults.
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Affiliation(s)
- Dong Liu
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China; School of Public Health, Nantong University, Nantong, China
| | - Siyue Tan
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Zhengyuan Zhou
- Department of Chronic Disease Control and Prevention, Changshu Center for Disease Control and Prevention, Suzhou, China
| | - Shujun Gu
- Department of Chronic Disease Control and Prevention, Changshu Center for Disease Control and Prevention, Suzhou, China.
| | - Hui Zuo
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China; MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, China.
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Zhang J, Ling L, Xiang L, Li W, Bao P, Yue W. Role of the gut microbiota in complications after ischemic stroke. Front Cell Infect Microbiol 2024; 14:1334581. [PMID: 38644963 PMCID: PMC11026644 DOI: 10.3389/fcimb.2024.1334581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.
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Affiliation(s)
- Jinwei Zhang
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Ling Ling
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
| | - Lei Xiang
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
| | - Wenxia Li
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Pengnan Bao
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Wei Yue
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
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20
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Fan X, Cao J, Li M, Zhang D, El‐Battrawy I, Chen G, Zhou X, Yang G, Akin I. Stroke Related Brain-Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2307698. [PMID: 38308187 PMCID: PMC11005719 DOI: 10.1002/advs.202307698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 01/09/2024] [Indexed: 02/04/2024]
Abstract
The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between the brain and heart. Post AIS, the ensuing cardiovascular dysfunctions encompass a spectrum of complications, including heart attack, congestive heart failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all of which are correlated with adverse outcomes and mortality. Mounting evidence underscores the intimate crosstalk between the heart and the brain, facilitated by intricate physiological and neurohumoral complex networks. The primary pathophysiological mechanisms contributing to these severe cardiac complications involve the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic and parasympathetic hyperactivity, immune and inflammatory responses, and gut dysbiosis, collectively shaping the stroke-related brain-heart axis. Ongoing research endeavors are concentrated on devising strategies to prevent AIS-induced cardiovascular dysfunctions. Notably, labetalol, nicardipine, and nitroprusside are recommended for hypertension control, while β-blockers are employed to avert chronic remodeling and address arrhythmias. However, despite these therapeutic interventions, therapeutic targets remain elusive, necessitating further investigations into this complex challenge. This review aims to delineate the state-of-the-art pathophysiological mechanisms in AIS through preclinical and clinical research, unraveling their intricate interplay within the brain-heart axis, and offering pragmatic suggestions for managing AIS-induced cardiovascular dysfunctions.
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Affiliation(s)
- Xuehui Fan
- Key Laboratory of Medical ElectrophysiologyMinistry of Education and Medical Electrophysiological Key Laboratory of Sichuan ProvinceCollaborative Innovation Center for Prevention of Cardiovascular DiseasesInstitute of Cardiovascular ResearchSouthwest Medical UniversityLuzhou646000China
- CardiologyAngiologyHaemostaseologyand Medical Intensive CareMedical Centre MannheimMedical Faculty MannheimHeidelberg University68167HeidelbergGermany
- European Center for AngioScience (ECAS)German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheimand Centre for Cardiovascular Acute Medicine Mannheim (ZKAM)Medical Centre MannheimHeidelberg University68167HeidelbergGermany
| | - Jianyang Cao
- School of Physical EducationSouthwest Medical UniversityLuzhouSichuan Province646000China
- Acupuncture and Rehabilitation DepartmentThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou646000China
| | - Mingxia Li
- School of Physical EducationSouthwest Medical UniversityLuzhouSichuan Province646000China
- Acupuncture and Rehabilitation DepartmentThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou646000China
| | - Dechou Zhang
- Department of NeurologyThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou646000China
| | - Ibrahim El‐Battrawy
- Department of Cardiology and AngiologyRuhr University44780BochumGermany
- Institut für Forschung und Lehre (IFL)Department of Molecular and Experimental CardiologyRuhr‐University Bochum44780BochumGermany
| | - Guiquan Chen
- Acupuncture and Rehabilitation DepartmentThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou646000China
| | - Xiaobo Zhou
- Key Laboratory of Medical ElectrophysiologyMinistry of Education and Medical Electrophysiological Key Laboratory of Sichuan ProvinceCollaborative Innovation Center for Prevention of Cardiovascular DiseasesInstitute of Cardiovascular ResearchSouthwest Medical UniversityLuzhou646000China
- CardiologyAngiologyHaemostaseologyand Medical Intensive CareMedical Centre MannheimMedical Faculty MannheimHeidelberg University68167HeidelbergGermany
- European Center for AngioScience (ECAS)German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheimand Centre for Cardiovascular Acute Medicine Mannheim (ZKAM)Medical Centre MannheimHeidelberg University68167HeidelbergGermany
| | - Guoqiang Yang
- CardiologyAngiologyHaemostaseologyand Medical Intensive CareMedical Centre MannheimMedical Faculty MannheimHeidelberg University68167HeidelbergGermany
- European Center for AngioScience (ECAS)German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheimand Centre for Cardiovascular Acute Medicine Mannheim (ZKAM)Medical Centre MannheimHeidelberg University68167HeidelbergGermany
- Acupuncture and Rehabilitation DepartmentThe Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou646000China
| | - Ibrahim Akin
- CardiologyAngiologyHaemostaseologyand Medical Intensive CareMedical Centre MannheimMedical Faculty MannheimHeidelberg University68167HeidelbergGermany
- European Center for AngioScience (ECAS)German Center for Cardiovascular Research (DZHK) Partner Site Heidelberg/Mannheimand Centre for Cardiovascular Acute Medicine Mannheim (ZKAM)Medical Centre MannheimHeidelberg University68167HeidelbergGermany
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21
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Hastings MH, Castro C, Freeman R, Abdul Kadir A, Lerchenmüller C, Li H, Rhee J, Roh JD, Roh K, Singh AP, Wu C, Xia P, Zhou Q, Xiao J, Rosenzweig A. Intrinsic and Extrinsic Contributors to the Cardiac Benefits of Exercise. JACC Basic Transl Sci 2024; 9:535-552. [PMID: 38680954 PMCID: PMC11055208 DOI: 10.1016/j.jacbts.2023.07.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 07/06/2023] [Accepted: 07/20/2023] [Indexed: 05/01/2024]
Abstract
Among its many cardiovascular benefits, exercise training improves heart function and protects the heart against age-related decline, pathological stress, and injury. Here, we focus on cardiac benefits with an emphasis on more recent updates to our understanding. While the cardiomyocyte continues to play a central role as both a target and effector of exercise's benefits, there is a growing recognition of the important roles of other, noncardiomyocyte lineages and pathways, including some that lie outside the heart itself. We review what is known about mediators of exercise's benefits-both those intrinsic to the heart (at the level of cardiomyocytes, fibroblasts, or vascular cells) and those that are systemic (including metabolism, inflammation, the microbiome, and aging)-highlighting what is known about the molecular mechanisms responsible.
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Affiliation(s)
- Margaret H. Hastings
- Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Claire Castro
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rebecca Freeman
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Azrul Abdul Kadir
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Carolin Lerchenmüller
- Department of Cardiology, University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, Germany
| | - Haobo Li
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - James Rhee
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Department of Anesthesiology and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jason D. Roh
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kangsan Roh
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Department of Anesthesiology and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anand P. Singh
- Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Chao Wu
- Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Peng Xia
- Cardiovascular Research Center, Division of Cardiology, Corrigan Minehan Heart Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Qiulian Zhou
- Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Junjie Xiao
- Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China
| | - Anthony Rosenzweig
- Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, Michigan, USA
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22
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Fu Y, Hou X, Feng Z, Feng H, Li L. Research progress in the relationship between gut microbiota metabolite trimethylamine N-oxide and ischemic stroke. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2024; 49:447-456. [PMID: 38970519 PMCID: PMC11208405 DOI: 10.11817/j.issn.1672-7347.2024.230427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Indexed: 07/08/2024]
Abstract
Ischemic stroke (IS) is a severe cerebrovascular disease that seriously endangers human health. Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine. In recent years, trimethylamine N-oxide (TMAO) as a gut microbiota metabolite has received widespread attention in cardiovascular diseases. Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis, atrial fibrillation, hypertension, and type 2 diabetes. TMAO exacerbates neurological damage in IS patients, increases the risk of IS recurrence, and is an independent predictor of post-stroke cognitive impairment (PSCI) in patients. Current research suggests that the mechanisms of TMAO action include endothelial dysfunction, promoting of foam cell formation, influence on cholesterol metabolism, and enhancement of platelet reactivity. Lowering plasma TMAO levels through the rational use of traditional Chinese medicine, dietary management, vitamins, and probiotics can prevent and treat IS.
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Affiliation(s)
- Yu Fu
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355.
| | - Xiaoqian Hou
- Department of Rehabilitation Medicine, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China
| | - Ziyun Feng
- Department of Rehabilitation Medicine, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China
| | - Huiyue Feng
- School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355
| | - Li Li
- Department of Rehabilitation Medicine, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China.
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23
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Florea CM, Rosu R, Moldovan R, Vlase L, Toma V, Decea N, Baldea I, Filip GA. The impact of chronic Trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis. Food Chem Toxicol 2024; 184:114429. [PMID: 38176578 DOI: 10.1016/j.fct.2023.114429] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/20/2023] [Accepted: 12/28/2023] [Indexed: 01/06/2024]
Abstract
TMAO, a gut microbiota derived byproduct, has been associated with various cardiometabolic diseases by promoting oxidative stress and inflammation. The liver is the main organ for TMAO production and chronic exposure to high doses of TMAO could alter its function. In this study, we evaluated the effect of chronic exposure of high TMAO doses on liver oxidative stress, inflammation, and fibrosis. TMAO was administered daily via gastric gavage to laboratory rats for 3 months. Blood was drawn for the quantification of TMAO, and liver tissues were harvested for the assessment of oxidative stress (MDA, GSH, GSSG, GPx, CAT, and 8-oxo-dG) and inflammation by quantification of IL-1α, TNF-α, IL-10, TGF-β, NOS and COX-2 expression. The evaluation of fibrosis was made by Western blot analysis of α-SMA and Collagen-3 protein expression. Histological investigation and immunohistochemical staining of iNOS were performed in order to assess the liver damage. After 3 months of TMAO exposure, TMAO serum levels enhanced in parallel with increases in MDA and GSSG levels in liver tissue and lower values of GSH and GSH/GSSG ratio as well as a decrease in GPx and CAT activities. Inflammation was also highlighted, with enhanced iNOS, COX-2, and IL-10 expression, without structural changes and without induction of liver fibrosis.
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Affiliation(s)
- Cristian Marius Florea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Radu Rosu
- Fifth Department of Internal Medicine, Cardiology Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Remus Moldovan
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Laurian Vlase
- Department of Pharmaceutical Technology and Biopharmaceutics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Vlad Toma
- Department of Molecular Biology and Biotechnologies, Faculty of Biology and Geology, Babeș-Bolyai University, Cluj-Napoca, Romania; Department of Experimental Biology and Biochemistry, Institute of Biological Research, branch of NIRDBS, Cluj-Napoca, Romania; Center for Systems Biology, Biodiversity and Bioresources "3B", Babeș-Bolyai University, Cluj-Napoca, Romania.
| | - Nicoleta Decea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ioana Baldea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Gabriela Adriana Filip
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Li K, Liu P, Liu M, Ye J, Zhu L. Putative causal relations among gut flora, serums metabolites and arrhythmia: a Mendelian randomization study. BMC Cardiovasc Disord 2024; 24:38. [PMID: 38212687 PMCID: PMC10782588 DOI: 10.1186/s12872-023-03703-z] [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: 11/19/2023] [Accepted: 12/31/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. METHODS Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. RESULTS Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. CONCLUSION This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.
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Affiliation(s)
- Kaiyuan Li
- Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China
- Department of Cardiovascular Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, No. 399 Hailing South Road, Taizhou, Jiangsu Province, China
| | - Peng Liu
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Miao Liu
- Department of Cardiovascular Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jun Ye
- Department of Cardiovascular Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, No. 399 Hailing South Road, Taizhou, Jiangsu Province, China
| | - Li Zhu
- Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China.
- Department of Cardiovascular Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, No. 399 Hailing South Road, Taizhou, Jiangsu Province, China.
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25
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Yang Y, Li X, Wang P, Shu S, Liu B, Liang Y, Yang B, Zhao Z, Luo Q, Liu Z, Zheng L, Zeng Q, Xiong C. The significance of dynamic monitoring plasma TMAO level in pulmonary arterial hypertension - a cohort study. Ther Adv Respir Dis 2024; 18:17534666231224692. [PMID: 38205629 PMCID: PMC10785727 DOI: 10.1177/17534666231224692] [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: 05/31/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive. OBJECTIVES To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis. DESIGN Single-center cohort study. METHODS Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events. RESULTS A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 μmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05). CONCLUSION Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.
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Affiliation(s)
- Yicheng Yang
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Li
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peizhi Wang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Songren Shu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bingyang Liu
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanru Liang
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Beilan Yang
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhihui Zhao
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qin Luo
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhihong Liu
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lemin Zheng
- The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Health Science Center, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100083, China
- China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing 100050, China
| | - Qixian Zeng
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 North Lishi Road, Xicheng District, Beijing 100037, China
| | - Changming Xiong
- Center of Respiratory and Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 North Lishi Road, Xicheng District, Beijing 100037, China
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26
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Tu R, Xia J. Stroke and Vascular Cognitive Impairment: The Role of Intestinal Microbiota Metabolite TMAO. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2024; 23:102-121. [PMID: 36740795 DOI: 10.2174/1871527322666230203140805] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 11/18/2022] [Accepted: 12/12/2022] [Indexed: 02/07/2023]
Abstract
The gut microbiome interacts with the brain bidirectionally through the microbiome-gutbrain axis, which plays a key role in regulating various nervous system pathophysiological processes. Trimethylamine N-oxide (TMAO) is produced by choline metabolism through intestinal microorganisms, which can cross the blood-brain barrier to act on the central nervous system. Previous studies have shown that elevated plasma TMAO concentrations increase the risk of major adverse cardiovascular events, but there are few studies on TMAO in cerebrovascular disease and vascular cognitive impairment. This review summarized a decade of research on the impact of TMAO on stroke and related cognitive impairment, with particular attention to the effects on vascular cognitive disorders. We demonstrated that TMAO has a marked impact on the occurrence, development, and prognosis of stroke by regulating cholesterol metabolism, foam cell formation, platelet hyperresponsiveness and thrombosis, and promoting inflammation and oxidative stress. TMAO can also influence the cognitive impairment caused by Alzheimer's disease and Parkinson's disease via inducing abnormal aggregation of key proteins, affecting inflammation and thrombosis. However, although clinical studies have confirmed the association between the microbiome-gut-brain axis and vascular cognitive impairment (cerebral small vessel disease and post-stroke cognitive impairment), the molecular mechanism of TMAO has not been clarified, and TMAO precursors seem to play the opposite role in the process of poststroke cognitive impairment. In addition, several studies have also reported the possible neuroprotective effects of TMAO. Existing therapies for these diseases targeted to regulate intestinal flora and its metabolites have shown good efficacy. TMAO is probably a new target for early prediction and treatment of stroke and vascular cognitive impairment.
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Affiliation(s)
- Ruxin Tu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
| | - Jian Xia
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
- Human Clinical Research Center for Cerebrovascular Disease, Changsha, China
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27
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Joerger AK, Albrecht C, Rothhammer V, Neuhaus K, Wagner A, Meyer B, Wostrack M. The Role of Gut and Oral Microbiota in the Formation and Rupture of Intracranial Aneurysms: A Literature Review. Int J Mol Sci 2023; 25:48. [PMID: 38203219 PMCID: PMC10779325 DOI: 10.3390/ijms25010048] [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: 11/12/2023] [Revised: 12/14/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
In recent years, there has been a growing interest in the role of the microbiome in cardiovascular and cerebrovascular diseases. Emerging research highlights the potential role of the microbiome in intracranial aneurysm (IA) formation and rupture, particularly in relation to inflammation. In this review, we aim to explore the existing literature regarding the influence of the gut and oral microbiome on IA formation and rupture. In the first section, we provide background information, elucidating the connection between inflammation and aneurysm formation and presenting potential mechanisms of gut-brain interaction. Additionally, we explain the methods for microbiome analysis. The second section reviews existing studies that investigate the relationship between the gut and oral microbiome and IAs. We conclude with a prospective overview, highlighting the extent to which the microbiome is already therapeutically utilized in other fields. Furthermore, we address the challenges associated with the context of IAs that still need to be overcome.
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Affiliation(s)
- Ann-Kathrin Joerger
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany; (A.-K.J.); (B.M.)
| | - Carolin Albrecht
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany; (A.-K.J.); (B.M.)
| | - Veit Rothhammer
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen Nuremberg, 91054 Erlangen, Germany;
| | - Klaus Neuhaus
- Core Facility Microbiom, ZIEL Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany;
| | - Arthur Wagner
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany; (A.-K.J.); (B.M.)
| | - Bernhard Meyer
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany; (A.-K.J.); (B.M.)
| | - Maria Wostrack
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University, 81675 Munich, Germany; (A.-K.J.); (B.M.)
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28
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Zhang W, Dong XY, Huang R. Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites. Transl Stroke Res 2023; 14:811-828. [PMID: 36279071 DOI: 10.1007/s12975-022-01096-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 09/05/2022] [Accepted: 10/07/2022] [Indexed: 11/30/2022]
Abstract
Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS.
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Affiliation(s)
- Wei Zhang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao Yu Dong
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Rui Huang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
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Hu X, Ren H, Cao Y. The association between trimethylamine N-oxide levels and ischemic stroke occurrence: a meta-analysis and Mendelian randomization study. BMC Neurol 2023; 23:413. [PMID: 37990303 PMCID: PMC10662484 DOI: 10.1186/s12883-023-03458-2] [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: 09/18/2023] [Accepted: 11/07/2023] [Indexed: 11/23/2023] Open
Abstract
BACKGROUND Trimethylamine-N-oxide (TMAO), an intestinal microbiota-derived choline metabolite, has been found to be associated with ischemic stroke (IS) in more and more studies. However, the causal role of TMAO on IS occurrence remains perplexing. METHODS We comprehensively screened the related clinical studies on PubMed, Web of Science, and Embase. Case-control and cohort studies that reported the TMAO levels of both IS patients and healthy controls were included, and the risk of bias was assessed according to the criteria by the Centre for Evidence-Based Medicine in Oxford, UK. A meta-analysis of the retrieved publications was performed with a random-effect model to analyze the connection between TMAO levels and IS events. Besides, a Mendelian randomization (MR) analysis was performed to study the causal effect of TMAO on IS, with pooled data of TMAO and IS obtained from genome-wide association studies (GWAS). The following methods were used: MR-Egger, weighted median, inverse-variance weighted, simple mode, and weighted mode. The study has been registered in INPLASY (Registration number: INPLASY2023100027). RESULTS Eight cohort or case-control studies covering 2444 cases and 1707 controls were identified. The pooled data indicated that the IS patients tended to have higher TMAO levels compared with the controls (mean difference: 1.97 μM; 95% confidence interval [CI]: 0.87, 3.07; P = 0.0005), while distinctive heterogeneity (I2 = 96%, P < 0.00001) was observed. Sub-group analysis revealed that the heterogeneity of the studies might be derived from the studies themselves. However, no causal effect of TMAO on IS was observed (P > 0.05) in the Mendelian randomization analysis of this study. CONCLUSION We confirmed that IS patients tend to have higher TMAO levels than healthy individuals, while our findings of MR analysis did not support the causal role of TMAO in IS occurrence. Therefore, more studies are required for a better understanding of the relationship between TMAO levels and IS onset.
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Affiliation(s)
- Xinhua Hu
- Department of Neurology, People's Hospital of Xinjin District, Chengdu, China
| | - Haiyan Ren
- Department of Neurology, Shanghai Sixth People's Hospital Xuhui Branch Affiliated With Shanghai Jiao Tong University, Shanghai, China
| | - Yuan Cao
- Department of Neurology, People's Hospital of Xinjin District, Chengdu, China.
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Zhou Y, Chen Y, He H, Peng M, Zeng M, Sun H. The role of the indoles in microbiota-gut-brain axis and potential therapeutic targets: A focus on human neurological and neuropsychiatric diseases. Neuropharmacology 2023; 239:109690. [PMID: 37619773 DOI: 10.1016/j.neuropharm.2023.109690] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/17/2023] [Accepted: 08/19/2023] [Indexed: 08/26/2023]
Abstract
At present, a large number of relevant studies have suggested that the changes in gut microbiota are related to the course of nervous system diseases, and the microbiota-gut-brain axis is necessary for the proper functioning of the nervous system. Indole and its derivatives, as the products of the gut microbiota metabolism of tryptophan, can be used as ligands to regulate inflammation and autoimmune response in vivo. In recent years, some studies have found that the levels of indole and its derivatives differ significantly between patients with central nervous system diseases and healthy individuals, suggesting that they may be important mediators for the involvement of the microbiota-gut-brain axis in the disease course. Tryptophan metabolites produced by gut microbiota are involved in multiple physiological reactions, take indole for example, it participates in the process of inflammation and anti-inflammatory effects through various cellular physiological activities mediated by aromatic hydrocarbon receptors (AHR), which can influence a variety of neurological and neuropsychiatric diseases. This review mainly explores and summarizes the relationship between indoles and human neurological and neuropsychiatric disorders, including ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, cognitive impairment, depression and anxiety, and puts forward that the level of indoles can be regulated through various direct or indirect ways to improve the prognosis of central nervous system diseases and reverse the dysfunction of the microbiota-gut-brain axis. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".
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Affiliation(s)
- Yi Zhou
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Yue Chen
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Hui He
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Meichang Peng
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Meiqin Zeng
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Haitao Sun
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital and the Second Clinical Medical College, Southern Medical University, Guangzhou, 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, 510280, China.
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Lledós M, Prats-Sánchez L, Llucià-Carol L, Cárcel-Márquez J, Muiño E, Cullell N, Gallego-Fabrega C, Martín-Campos JM, Aguilera-Simón A, Guasch-Jiménez M, Guisado-Alonso D, Ramos-Pachón A, Martínez-Domeño A, Izquierdo A, Marín R, Camps-Renom P, Martí-Fàbregas J, Fernández-Cadenas I. Ischaemic stroke patients present sex differences in gut microbiota. Eur J Neurol 2023; 30:3497-3506. [PMID: 37329328 DOI: 10.1111/ene.15931] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 06/07/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND Gut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut-brain axis. Nevertheless, little is known about sex-specific microbiota signatures in IS occurrence. METHODS A total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two-sample Mendelian randomisation (MR) with inverse-variance weighting (IVW) using genome-wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively. RESULTS α-Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance-based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex-differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni-corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, β = 0.32). CONCLUSIONS Our study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.
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Affiliation(s)
- Miquel Lledós
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
- Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Barcelona, Spain
| | - Luís Prats-Sánchez
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Laia Llucià-Carol
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Jara Cárcel-Márquez
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Elena Muiño
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Natalia Cullell
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
- Stroke Pharmacogenomics and Genetics Laboratory, Fundación Docència i Recerca MútuaTerrassa, Hospital Mútua de Terrassa, Terrassa, Spain
| | - Cristina Gallego-Fabrega
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Jesús M Martín-Campos
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
| | - Ana Aguilera-Simón
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Marina Guasch-Jiménez
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Daniel Guisado-Alonso
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Anna Ramos-Pachón
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Artur Izquierdo
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Rebeca Marín
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Pol Camps-Renom
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Joan Martí-Fàbregas
- Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Israel Fernández-Cadenas
- Stroke Pharmacogenomics and Genetics Laboratory, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain
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Jiao Y, Li W, Zhang Q, Jiang Q. Gut microbiota and hypertension: a bibliometric analysis of recent research (2014-2023). Front Nutr 2023; 10:1253803. [PMID: 37899834 PMCID: PMC10602761 DOI: 10.3389/fnut.2023.1253803] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 08/31/2023] [Indexed: 10/31/2023] Open
Abstract
Background Cardiovascular diseases persist as the primary cause of mortality in the global population. Hypertension (HTN) is widely recognized as one of the most crucial risk factors contributing to severe cardiovascular conditions. In recent years, a growing body of research has highlighted the therapeutic potential of gut microbiota (GM) in addressing cardiovascular diseases, particularly HTN. Consequently, unraveling and synthesizing the connections between GM and HTN, key research domains, and the underlying interaction mechanisms have grown increasingly vital. Methods We retrieved articles related to GM and HTN from 2014 to 2023 using Web of Science. Bibliometric tools employed in this analysis include CiteSpace and VOSviewer. Result From 2014 to 2023, we identified 1,730 related articles. These articles involved 88 countries (regions) and 9,573 authors. The articles were published in 593 journals, with 1000 references exhibiting co-occurrence more than 10 times. The number of studies in this field has been increasing, indicating that it remains a research hotspot. We expect this field to continue gaining attention in the future. China leads in the number of published articles, while the United States boasts the most extensive international collaborations, signifying its continued prominence as a research hub in this domain. Tain You-Lin, Hsu Chien-Ning, Raizada Mohan K, and Yang Tao are among the authors with the highest publication volume. Publications in this field are frequently found in nutrition, cardiovascular, and molecular biology journals. The most frequently occurring keywords include metabolic syndrome, cardiovascular disease, inflammation, short-chain fatty acids, trimethylamine N-oxide, chronic kidney disease, heart failure, and high-salt diet. Conclusion The relationship between GM and HTN is presently one of the most active research areas. By employing bibliometric tools, we analyzed critical and innovative articles in this field to provide an objective summary of the primary research directions, such as the relationship between GM and HTN, GM metabolites, high-salt diet, the developmental origins of health and disease, obstructive sleep apnea-Induced hypertension and antihypertensive peptide. Our analysis aims to offer researchers insights into hotspots and emerging trends in the field of GM and HTN for future research reference.
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Affiliation(s)
- Yang Jiao
- Department of Cardiology, Zunyi First People's Hospital, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Wenxing Li
- Department of Cardiology, Zunyi First People's Hospital, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- Zunyi Medical University, Zunyi, Guizhou, China
| | - Qianyi Zhang
- Department of Cardiology, Zunyi First People's Hospital, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- Zunyi Medical University, Zunyi, Guizhou, China
| | - Qianfeng Jiang
- Department of Cardiology, Guizhou Aerospace Hospital, Zunyi, Guizhou, China
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Mihuta MS, Paul C, Borlea A, Roi CM, Pescari D, Velea-Barta OA, Mozos I, Stoian D. Connections between serum Trimethylamine N-Oxide (TMAO), a gut-derived metabolite, and vascular biomarkers evaluating arterial stiffness and subclinical atherosclerosis in children with obesity. Front Endocrinol (Lausanne) 2023; 14:1253584. [PMID: 37850094 PMCID: PMC10577381 DOI: 10.3389/fendo.2023.1253584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 09/12/2023] [Indexed: 10/19/2023] Open
Abstract
Introduction Childhood obesity leads to early subclinical atherosclerosis and arterial stiffness. Studying biomarkers like trimethylamine N-oxide (TMAO), linked to cardio-metabolic disorders in adults, is crucial to prevent long-term cardiovascular issues. Methods The study involved 70 children aged 4 to 18 (50 obese, 20 normal-weight). Clinical examination included BMI, waist measurements, puberty stage, the presence of acanthosis nigricans, and irregular menstrual cycles. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (CIMT), and the arterial stiffness was evaluated through surrogate markers like the pulse wave velocity (PWV), augmentation index (AIx), and peripheral and central blood pressures. The blood biomarkers included determining the values of TMAO, HOMA-IR, and other usual biomarkers investigating metabolism. Results The study detected significantly elevated levels of TMAO in obese children compared to controls. TMAO presented positive correlations to BMI, waist circumference and waist-to-height ratio and was also observed as an independent predictor of all three parameters. Significant correlations were observed between TMAO and vascular markers such as CIMT, PWV, and peripheral BP levels. TMAO independently predicts CIMT, PWV, peripheral BP, and central SBP levels, even after adding BMI, waist circumference, waist-to-height ratio, puberty development and age in the regression model. Obese children with high HOMA-IR presented a greater weight excess and significantly higher vascular markers, but TMAO levels did not differ significantly from the obese with HOMA-IR Conclusion Our study provides compelling evidence supporting the link between serum TMAO, obesity, and vascular damage in children. These findings highlight the importance of further research to unravel the underlying mechanisms of this connection.
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Affiliation(s)
- Monica Simina Mihuta
- Department of Doctoral Studies, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Corina Paul
- Department of Pediatrics, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Andreea Borlea
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
- 2nd Department of Internal Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Cristina Mihaela Roi
- Department of Doctoral Studies, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Denisa Pescari
- Department of Doctoral Studies, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Oana-Alexandra Velea-Barta
- 3rd Department of Odontotherapy and Endodontics, Faculty of Dental Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Ioana Mozos
- Department of Functional Sciences—Pathophysiology, Center for Translational Research and Systems Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Dana Stoian
- Center of Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
- 2nd Department of Internal Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
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Jeong S, Chokkalla AK, Davis CK, Vemuganti R. Post-stroke depression: epigenetic and epitranscriptomic modifications and their interplay with gut microbiota. Mol Psychiatry 2023; 28:4044-4055. [PMID: 37188778 PMCID: PMC10646155 DOI: 10.1038/s41380-023-02099-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 04/21/2023] [Accepted: 05/02/2023] [Indexed: 05/17/2023]
Abstract
Epigenetic and epitranscriptomic modifications that regulate physiological processes of an organism at the DNA and RNA levels, respectively, are novel therapeutic candidates for various neurological diseases. Gut microbiota and its metabolites are known to modulate DNA methylation and histone modifications (epigenetics), as well as RNA methylation especially N6-methyladenosine (epitranscriptomics). As gut microbiota as well as these modifications are highly dynamic across the lifespan of an organism, they are implicated in the pathogenesis of stroke and depression. The lack of specific therapeutic interventions for managing post-stroke depression emphasizes the need to identify novel molecular targets. This review highlights the interaction between the gut microbiota and epigenetic/epitranscriptomic pathways and their interplay in modulating candidate genes that are involved in post-stroke depression. This review further focuses on the three candidates, including brain-derived neurotrophic factor, ten-eleven translocation family proteins, and fat mass and obesity-associated protein based on their prevalence and pathoetiologic role in post-stroke depression.
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Affiliation(s)
- Soomin Jeong
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
- Neuroscience Training Program, University of Wisconsin, Madison, WI, USA
| | - Anil K Chokkalla
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
| | - Charles K Davis
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA
| | - Raghu Vemuganti
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
- Neuroscience Training Program, University of Wisconsin, Madison, WI, USA.
- William S. Middleton Veterans Hospital, Madison, WI, USA.
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Cheng H, Zhang D, Wu J, Liu J, Zhou Y, Tan Y, Feng W, Peng C. Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:154979. [PMID: 37552899 DOI: 10.1016/j.phymed.2023.154979] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/30/2023] [Accepted: 07/15/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. OBJECTIVES This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. METHODS We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and β-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. CONCLUSION The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.
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Affiliation(s)
- Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Jing Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Juan Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, PR China
| | - Yaochuan Zhou
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
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Xie H, Chen J, Chen Q, Zhao Y, Liu J, Sun J, Hu X. The Diagnostic Value of Gut Microbiota Analysis for Post-Stroke Sleep Disorders. Diagnostics (Basel) 2023; 13:2970. [PMID: 37761337 PMCID: PMC10530055 DOI: 10.3390/diagnostics13182970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Gut microbiota have been associated with many psychiatric disorders. However, the changes in the composition of gut microbiota in patients with post-stroke sleep disorders (PSSDs) remain unclear. Here, we determined the gut microbial signature of PSSD patients. METHODS Fecal samples of 205 patients with ischemic stroke were collected within 24 h of admission and were further analyzed using 16 s RNA gene sequencing followed by bioinformatic analysis. The diversity, community composition, and differential microbes of gut microbiota were assessed. The outcome of sleep disorders was determined by the Pittsburgh Sleep Quality Index (PSQI) at 3 months after admission. The diagnostic performance of microbial characteristics in predicting PSSDs was assessed by receiver operating characteristic (ROC) curves. RESULTS Our results showed that the composition and structure of microbiota in patients with PSSDs were different from those without sleep disorders (PSNSDs). Moreover, the linear discriminant analysis effect size (LEfSe) showed significant differences in gut-associated bacteria, such as species of Streptococcus, Granulicatella, Dielma, Blautia, Paeniclostridium, and Sutterella. We further managed to identify the optimal microbiota signature and revealed that the predictive model with eight operational-taxonomic-unit-based biomarkers achieved a high accuracy in PSSD prediction (AUC = 0.768). Blautia and Streptococcus were considered to be the key microbiome signatures for patients with PSSD. CONCLUSIONS These findings indicated that a specific gut microbial signature was an important predictor of PSSDs, which highlighted the potential of microbiota as a promising biomarker for detecting PSSD patients.
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Affiliation(s)
- Huijia Xie
- Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; (H.X.); (J.C.); (Q.C.); (Y.Z.)
| | - Jiaxin Chen
- Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; (H.X.); (J.C.); (Q.C.); (Y.Z.)
| | - Qionglei Chen
- Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; (H.X.); (J.C.); (Q.C.); (Y.Z.)
| | - Yiting Zhao
- Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; (H.X.); (J.C.); (Q.C.); (Y.Z.)
| | - Jiaming Liu
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China;
| | - Jing Sun
- Department of Geriatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; (H.X.); (J.C.); (Q.C.); (Y.Z.)
| | - Xuezhen Hu
- Department of Emergency Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China
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Castillo P, Kuda O, Kopecky J, Pomar CA, Palou A, Palou M, Picó C. Stachydrine, N-acetylornithine and trimethylamine N-oxide levels as candidate milk biomarkers of maternal consumption of an obesogenic diet during lactation. Biofactors 2023; 49:1022-1037. [PMID: 37227188 DOI: 10.1002/biof.1974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 05/04/2023] [Indexed: 05/26/2023]
Abstract
We aimed to evaluate whether improving maternal diet during lactation in diet-induced obese rats reverts the impact of western diet (WD) consumption on the metabolome of milk and offspring plasma, as well as to identify potential biomarkers of these conditions. Three groups of dams were followed: control-dams (CON-dams), fed with standard diet (SD); WD-dams, fed with WD prior and during gestation and lactation; and reversion-dams (REV-dams), fed as WD-dams but moved to SD during lactation. Metabolomic analysis was performed in milk at lactation days 5, 10, and 15, and in plasma from their male and female offspring at postnatal day 15. Milk of WD-dams presented, throughout lactation and compared to CON-dams, altered profiles of amino acids and of the carnitine pool, accompanied by changes in other polar metabolites, being stachydrine, N-acetylornithine, and trimethylamine N-oxide the most relevant and discriminatory metabolites between groups. The plasma metabolome profile was also altered in the offspring of WD-dams in a sex-dependent manner, and stachydrine, ergothioneine and the acylcarnitine C12:1 appeared as the top three most discriminating metabolites in both sexes. Metabolomic changes were largely normalized to control levels both in the milk of REV-dams and in the plasma of their offspring. We have identified a set of polar metabolites in maternal milk and in the plasma of the offspring whose alterations may indicate maternal intake of an unbalanced diet during gestation and lactation. Levels of these metabolites may also reflect the beneficial effects of implementing a healthier diet during lactation.
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Affiliation(s)
- Pedro Castillo
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation) of the University of the Balearic Islands, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Ondrej Kuda
- Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
| | - Jan Kopecky
- Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
| | - Catalina Amadora Pomar
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation) of the University of the Balearic Islands, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Andreu Palou
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation) of the University of the Balearic Islands, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Mariona Palou
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation) of the University of the Balearic Islands, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Catalina Picó
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation) of the University of the Balearic Islands, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
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Kijpaisalratana N, Ament Z, Bevers MB, Bhave VM, Garcia Guarniz AL, Couch CA, Irvin MR, Kimberly WT. Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke. JAMA Netw Open 2023; 6:e2330446. [PMID: 37610752 PMCID: PMC10448304 DOI: 10.1001/jamanetworkopen.2023.30446] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/15/2023] [Indexed: 08/24/2023] Open
Abstract
Importance Although increasing evidence suggests that trimethylamine N-oxide (TMAO) is associated with atherosclerosis, little is known about whether TMAO and its related metabolites (ie, choline, betaine, and carnitine) are associated with small vessel disease. Objective To evaluate the association between TMAO and its related metabolites with features of cerebral small vessel disease, including white matter hyperintensity volume (WMHV) and acute lacunar infarction. Design, Setting, and Participants This cross-sectional study included patients enrolled in the Specialized Programs of Translational Research in Acute Stroke biorepository. The registry included 522 patients with acute ischemic stroke who were 18 years or older who presented at the Massachusetts General Hospital or Brigham and Women's Hospital within 9 hours after onset between January 2007 and April 2010. The analyses in this study were conducted between November 2022 and April 2023. Exposures Plasma TMAO, choline, betaine, and carnitine were measured by liquid chromatography-tandem mass spectrometry. Main Outcomes and Measures WMHV was quantified by a semiautomated approach using signal intensity threshold with subsequent manual editing. Ischemic stroke subtype was classified using the Causative Classification System. Results Among 351 patients included in this study, the mean (SD) age was 69 (15) years; 209 patients (59.5%) were male and had a median (IQR) admission National Institute of Health Stroke Scale of 6 (3-13). The magnetic resonance imaging subgroup consisted of 291 patients with a mean (SD) age of 67 (15) years. Among these, the median (IQR) WMHV was 3.2 (1.31-8.4) cm3. TMAO was associated with WMHV after adjustment for age and sex (β, 0.15; 95% CI, 0.01-0.29; P < .001). TMAO remained significant in a multivariate analysis adjusted for age, sex, hypertension, diabetes, and smoking (β, 0.14; 95% CI, 0-0.29; P = .05). TMAO was associated with lacunar stroke but not other ischemic stroke subtypes in a model adjusted for age, sex, hypertension, diabetes, and smoking (OR, 1.67; 95% CI, 1.05-2.66; P = .03). Conclusions and Relevance In this observational study, TMAO was associated with cerebral small vessel disease determined by WMHV and acute lacunar infarction. The association was independent of traditional vascular risk factors.
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Affiliation(s)
- Naruchorn Kijpaisalratana
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
- Department of Neurology, Massachusetts General Hospital, Boston
- Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Zsuzsanna Ament
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
- Department of Neurology, Massachusetts General Hospital, Boston
| | - Matthew B. Bevers
- Divisions of Stroke, Cerebrovascular and Critical Care Neurology, Brigham and Women’s Hospital, Boston, Massachusetts
| | | | | | - Catharine A. Couch
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham
| | - M. Ryan Irvin
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham
| | - W. Taylor Kimberly
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
- Department of Neurology, Massachusetts General Hospital, Boston
- Harvard Medical School, Boston, Massachusetts
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Chou PS, Yang IH, Kuo CM, Wu MN, Lin TC, Fong YO, Juan CH, Lai CL. The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke. Int J Mol Sci 2023; 24:10796. [PMID: 37445971 DOI: 10.3390/ijms241310796] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/13/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Bidirectional communication of the microbiota-gut-brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0-3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.
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Affiliation(s)
- Ping-Song Chou
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
- Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
| | - I-Hsiao Yang
- Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Chia-Ming Kuo
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Meng-Ni Wu
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Tzu-Chao Lin
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Yi-On Fong
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Chi-Hung Juan
- Institute of Cognitive Neuroscience, National Central University, Taoyuan City 320317, Taiwan
- Cognitive Intelligence and Precision Healthcare Research Center, National Central University, Taoyuan City 320317, Taiwan
| | - Chiou-Lian Lai
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
- Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
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40
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Han S, Cai L, Chen P, Kuang W. A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis. Front Microbiol 2023; 14:1191758. [PMID: 37350780 PMCID: PMC10282156 DOI: 10.3389/fmicb.2023.1191758] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/19/2023] [Indexed: 06/24/2023] Open
Abstract
Purpose This study intends to uncover a more thorough knowledge structure, research hotspots, and future trends in the field by presenting an overview of the relationship between stroke and gut microbiota in the past two decades. Method Studies on stroke and gut microbiota correlations published between 1st January 2002 and 31st December 2021 were retrieved from the Web of Science Core Collection and then visualized and scientometrically analyzed using CiteSpace V. Results A total of 660 papers were included in the study, among which the United States, the United Kingdom, and Germany were the leading research centers. Cleveland Clinic, Southern Medical University, and Chinese Academy of Science were the top three institutions. The NATURE was the most frequently co-cited journal. STANLEY L HAZEN was the most published author, and Tang WHW was the most cited one. The co-occurrence analysis revealed eight clusters (i.e., brain-gut microbiota axis, fecal microbiome transplantation, gut microbiota, hypertension, TMAO, ischemic stroke, neuroinflammation, atopobiosis). "gut microbiota," "Escherichia coli," "cardiovascular disease," "risk," "disease," "ischemic stroke," "stroke," "metabolism," "inflammation," and "phosphatidylcholine" were the most recent keyword explosions. Conclusion Findings suggest that in the next 10 years, the number of publications produced annually may increase significantly. Future research trends tend to concentrate on the mechanisms of stroke and gut microbiota, with the inflammation and immunological mechanisms, TMAO, and fecal transplantation as hotspots. And the relationship between these mechanisms and a particular cardiovascular illness may also be a future research trend.
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Affiliation(s)
- Shengnan Han
- Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Longhui Cai
- First School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Peipei Chen
- School of Medical Technology, Qiqihar Medical College, Qiqihar, Heilongjiang, China
| | - Weihong Kuang
- Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
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Zhang P, Wang R, Qu Y, Guo ZN, Yang Y. Gut microbiota-derived metabolite trimethylamine-N-oxide and stroke outcome: a systematic review. Front Mol Neurosci 2023; 16:1165398. [PMID: 37333616 PMCID: PMC10272813 DOI: 10.3389/fnmol.2023.1165398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 05/15/2023] [Indexed: 06/20/2023] Open
Abstract
Introduction The relationship between baseline trimethylamine N-oxide (TMAO) levels and stroke outcomes remains unclear. Therefore, this systematic review aimed to summarize the existing relevant research. Methods We searched for studies on the association between baseline plasma levels of TMAO and stroke outcomes in the PubMed, EMBASE, Web of Science, and Scopus databases from their inception to 12 October 2022. Two researchers independently reviewed the studies for inclusion and extracted the relevant data. Results Seven studies were included in the qualitative analysis. Among them, six studies reported the outcome of acute ischemic stroke (AIS) and one study of intracerebral hemorrhage (ICH), respectively. Furthermore, no study reported the outcome of subarachnoid hemorrhage. Among patients with AIS, high baseline TMAO levels were associated with unfavorable functional outcomes or mortality at 3 months, as well as a high hazard ratio of mortality, recurrence, or major adverse cardiac event. Moreover, TMAO levels showed predictive utility for unfavorable functional outcomes or mortality at 3 months. Among patients with ICH, high TMAO levels were associated with unfavorable functional outcomes at 3 months, regardless of whether the TMAO value was considered a continuous or a categorical variable. Conclusion Limited evidence indicates that high baseline plasma levels of TMAO may be associated with poor stroke outcomes. Further studies are warranted to confirm the relationship between TMAO and stroke outcomes.
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Affiliation(s)
- Peng Zhang
- Stroke Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
- Neuroscience Research Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
| | - Rui Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
- Department of Thoracic Surgery, First Hospital of Jilin University, Changchun, China
| | - Yang Qu
- Stroke Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
- Neuroscience Research Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
| | - Zhen-Ni Guo
- Stroke Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
- Neuroscience Research Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
| | - Yi Yang
- Stroke Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
- Neuroscience Research Center, Department of Neurology, First Hospital of Jilin University, Changchun, China
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Zhang S, Jin M, Ren J, Sun X, Zhang Z, Luo Y, Sun X. New insight into gut microbiota and their metabolites in ischemic stroke: A promising therapeutic target. Biomed Pharmacother 2023; 162:114559. [PMID: 36989717 DOI: 10.1016/j.biopha.2023.114559] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
The gut-brain axis has been shown to play a vital role in the prognosis and recovery of ischemic stroke (IS), which is associated with gut microbiota dysfunction and changes in the gastrointestinal system and epithelial barrier integrity. In turn, gut microbiota and its derived metabolites can influence stroke outcomes. In this review, we first describe the relationship between IS (clinical and experimental IS) and the gut microbiota. Second, we summarize the role and specific mechanisms of microbiota-derived metabolites in IS. Further, we discuss the roles of natural medicines targeting the gut microbiota. Finally, the potential use of the gut microbiota and derived metabolites as a promising therapeutic opportunity for stroke prevention, diagnosis, and treatment is explored.
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Kaur N, LaForce G, Mallela DP, Saha PP, Buffa J, Li XS, Sangwan N, Rothenberg K, Zhu W. Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia. Int J Mol Sci 2023; 24:ijms24098091. [PMID: 37175797 PMCID: PMC10178712 DOI: 10.3390/ijms24098091] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/27/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide (TMAO) pathway impacts stroke severity, both infarct size and long-term cognitive outcomes. However, the molecular mechanisms that underly the role of the microbiome in VaD have not been explored in depth. To address this issue, we performed a comprehensive RNA-sequencing analysis to identify differentially expressed (DE) genes in the ischemic cerebral cortex of mouse brains at pre-stroke and post-stroke day 1 and day 3. A total of 4016, 3752 and 7861 DE genes were identified at pre-stroke and post-stroke day 1 and day 3, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated pathways of neurodegeneration in multiple diseases, chemokine signaling, calcium signaling, and IL-17 signaling as the key enriched pathways. Inflammatory response genes interleukin-1 beta (Il-1β), chemokines (C-X-C motif chemokine ligand 10 (Cxcl10), chemokine ligand 2 (Ccl2)), and immune system genes (S100 calcium binding protein 8 (S100a8), lipocalin-2 (Lcn2)) were among the most significantly upregulated genes. Hypocretin neuropeptide precursor (Hcrt), a neuropeptide, and transcription factors such as neuronal PAS domain protein 4 (Npas4), GATA binding protein 3 (Gata3), and paired box 7 (Pax7) were among the most significantly downregulated genes. In conclusion, our results indicate that higher plasma TMAO levels induce differential mRNA expression profiles in the ischemic brain tissue in our pre-clinical stroke model, and the predicted pathways provide the molecular basis for regulating the TMAO-enhanced neuroinflammatory response in the brain.
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Affiliation(s)
- Navdeep Kaur
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Geneva LaForce
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Deepthi P Mallela
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Prasenjit Prasad Saha
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Jennifer Buffa
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Xinmin S Li
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Naseer Sangwan
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
- Microbial Sequencing & Analytics Resource (MSAAR) Facility, Shared Laboratory Resources (SLR), Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Kasia Rothenberg
- Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland, OH 44195, USA
| | - Weifei Zhu
- Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
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Florea CM, Baldea I, Rosu R, Moldovan R, Decea N, Filip GA. The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings. Cardiovasc Toxicol 2023:10.1007/s12012-023-09794-6. [PMID: 37119388 DOI: 10.1007/s12012-023-09794-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 04/24/2023] [Indexed: 05/01/2023]
Abstract
A growing body of evidence suggests that the gut microbiota affects the cardiovascular system directly and indirectly via biologically active molecules. TMAO, a key metabolite produced by gut bacteria is implicated in atherosclerosis and chronic endothelial dysfunction, but with an unclear effect on vascular tone, oxidative stress, and inflammation. Our study aimed to evaluate the acute effects of TMAO on vascular contractility in relation with oxidative stress markers and inflammation. Aortic rings were harvested from laboratory rats and placed in a tissue bath system containing TMAO in concentrations of 300, 100, 10 µM, and control. Vascular tone under the influence of vasoconstrictor phenylephrine and non-endothelial-dependent vasodilator sodium nitroprusside was assessed using force transducers connected to a computer-based acquisition system. Oxidative stress and inflammation were quantified by vascular assessment of the activity of NF-κB, NRF2, SOD1, and iNOS by western-blotting and MDA by spectrofluorimetry. After the incubation of the aortic rings in TMAO solutions for 1 h, there was no difference in vasoconstrictor and non-endothelial vasodilator response between the studied doses. TMAO acutely induced oxidative stress and inflammation, significantly increasing levels of MDA and the expression of NF-κB, NRF2, SOD1, and iNOS, mostly in a dose-dependent manner. Our study showed the lack of a short-term effect of studied TMAO doses on vascular contractility, but demonstrated an acute prooxidative effect and activation of major inflammatory pathways, which can partially explain the detrimental effects of TMAO in cardiovascular disease.
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Affiliation(s)
- Cristian Marius Florea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania
| | - Ioana Baldea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania.
| | - Radu Rosu
- Fifth Department of Internal Medicine, Cardiology Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Remus Moldovan
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania
| | - Nicoleta Decea
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania
| | - Gabriela Adriana Filip
- Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania
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Fan H, Liu X, Ren Z, Fei X, Luo J, Yang X, Xue Y, Zhang F, Liang B. Gut microbiota and cardiac arrhythmia. Front Cell Infect Microbiol 2023; 13:1147687. [PMID: 37180433 PMCID: PMC10167053 DOI: 10.3389/fcimb.2023.1147687] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 03/27/2023] [Indexed: 05/16/2023] Open
Abstract
One of the most prevalent cardiac diseases is cardiac arrhythmia, however the underlying causes are not entirely understood. There is a lot of proof that gut microbiota (GM) and its metabolites have a significant impact on cardiovascular health. In recent decades, intricate impacts of GM on cardiac arrythmia have been identified as prospective approaches for its prevention, development, treatment, and prognosis. In this review, we discuss about how GM and its metabolites might impact cardiac arrhythmia through a variety of mechanisms. We proposed to explore the relationship between the metabolites produced by GM dysbiosis including short-chain fatty acids(SCFA), Indoxyl sulfate(IS), trimethylamine N-oxide(TMAO), lipopolysaccharides(LPS), phenylacetylglutamine(PAGln), bile acids(BA), and the currently recognized mechanisms of cardiac arrhythmias including structural remodeling, electrophysiological remodeling, abnormal nervous system regulation and other disease associated with cardiac arrythmia, detailing the processes involving immune regulation, inflammation, and different types of programmed cell death etc., which presents a key aspect of the microbial-host cross-talk. In addition, how GM and its metabolites differ and change in atrial arrhythmias and ventricular arrhythmias populations compared with healthy people are also summarized. Then we introduced potential therapeutic strategies including probiotics and prebiotics, fecal microbiota transplantation (FMT) and immunomodulator etc. In conclusion, the GM has a significant impact on cardiac arrhythmia through a variety of mechanisms, offering a wide range of possible treatment options. The discovery of therapeutic interventions that reduce the risk of cardiac arrhythmia by altering GM and metabolites is a real challenge that lies ahead.
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Affiliation(s)
- Hongxuan Fan
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xuchang Liu
- Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Zhaoyu Ren
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaoning Fei
- Clinical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jing Luo
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xinyu Yang
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yaya Xue
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Fenfang Zhang
- Department of Cardiology, Yangquan First People’s Hospital, Yangquan, Shanxi, China
| | - Bin Liang
- Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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46
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MUHAMMAD M, MUCHIMAPURA S, WATTANATHORN J. Microbiota-gut-brain axis impairment in the pathogenesis of stroke: implication as a potent therapeutic target. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2023; 42:143-151. [PMID: 37404572 PMCID: PMC10315190 DOI: 10.12938/bmfh.2022-067] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 03/09/2023] [Indexed: 07/06/2023]
Abstract
The human microbiota-gut-brain axis has an enormous role in the maintenance of homeostasis and health. Over the last two decades, it has received concerted research attention and focus due to a rapidly emerging volume of evidence that has established that impairment within the microbiota-gut-brain axis contributes to the development and progression of various diseases. Stroke is one of the entities identified to be associated with microbiota-gut-brain axis impairment. Currently, there are still limitations in the clinical treatment of stroke, and the presence of a non-nervous factor from gut microbiota that can alter the course of stroke presents a novel strategy towards the search for a therapeutic silver bullet against stroke. Hence, the aim herein, was to focus on the involvement of microbiota-gut-brain axis impairment in the pathogenesis stroke as well as elucidate its implications as a potent therapeutic target against stroke. The findings of studies to date have revealed and extended the role microbiota-gut-brain axis impairment in the pathogenesis of stroke, and studies have identified from both clinical and pre-clinical perspectives targets within the microbiota-gut-brain axis and successfully modulated the outcome of stroke. It was concluded that the microbiota-gut-brain axis stands as potent target to salvage the neurons in the ischemic penumbra for the treatment of stroke. Assessment of the microbiota profile and its metabolites status holds enormous clinical potentials as a non-invasive indicator for the early diagnosis and prognosis of stroke.
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Affiliation(s)
- Mubarak MUHAMMAD
- Graduate School (Neuroscience Program), Faculty of Medicine,
Khon Kaen University, 123 Moo 16 Mittraphap Rd., Nai-Muang, Muang District, Khon Kaen
40002, Thailand
| | - Supaporn MUCHIMAPURA
- Department of Physiology, Faculty of Medicine, Khon Kaen
University, 123 Moo 16 Mittraphap Rd., Nai-Muang, Muang District, Khon Kaen 40002,
Thailand
- Integrative Complementary Alternative Medicine Research and
Development Center in the Research Institute for Human High Performance and Health
Promotion, Khon Kaen University, 123 Moo 16 Mittraphap Rd., Nai-Muang, Muang District,
Khon Kaen 40002, Thailand
| | - Jintanaporn WATTANATHORN
- Department of Physiology, Faculty of Medicine, Khon Kaen
University, 123 Moo 16 Mittraphap Rd., Nai-Muang, Muang District, Khon Kaen 40002,
Thailand
- Integrative Complementary Alternative Medicine Research and
Development Center in the Research Institute for Human High Performance and Health
Promotion, Khon Kaen University, 123 Moo 16 Mittraphap Rd., Nai-Muang, Muang District,
Khon Kaen 40002, Thailand
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47
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Wang X, Eguchi A, Fujita Y, Wan X, Chang L, Yang Y, Shan J, Qu Y, Ma L, Shirayama Y, Mori C, Yang J, Hashimoto K. Abnormal compositions of gut microbiota and metabolites are associated with susceptibility versus resilience in rats to inescapable electric stress. J Affect Disord 2023; 331:369-379. [PMID: 36972851 DOI: 10.1016/j.jad.2023.03.073] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/30/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Increasing evidence suggests the role of gut microbiota in resilience versus vulnerability after stress. However, the role of gut microbiota and microbiome-derived metabolites in resilience versus susceptibility in rodents exposed to stress remains unclear. METHODS Adult male rats were exposed to inescapable electric stress under the learned helplessness (LH) paradigm. The composition of gut microbiota and metabolites in the brain and blood from control (no stress) rats, LH resilient rats, and LH susceptible rats were examined. RESULTS At the genus level, the relative abundances of Asaccharobacter, Eisenbergiella, and Klebsiella in LH susceptible rats were significantly higher than that of LH resilient rats. At the species level, the relative abundances of several microbiome were significantly altered between LH susceptible rats and LH resilient rats. Furthermore, there were several metabolites in the brain and blood altered between LH susceptible rats and LH resilient rats. A network analysis showed correlations between the abundance of several microbiome and metabolites in the brain (or blood). LIMITATIONS Detailed roles of microbiome and metabolites are unclear. CONCLUSIONS These findings suggest that abnormal compositions of the gut microbiota and metabolites might contribute to susceptibility versus resilience in rats subjected to inescapable electric foot shock.
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Affiliation(s)
- Xingming Wang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
| | - Akifumi Eguchi
- Department of Sustainable Health Science, Chiba University Center for Preventive Medical Sciences, Chiba 263-8522, Japan
| | - Yuko Fujita
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Xiayun Wan
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Lijia Chang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Yong Yang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Jiajing Shan
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Youge Qu
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Li Ma
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Yukihiko Shirayama
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Psychiatry, Teikyo University Chiba Medical Center, Ichihara 299-0111, Japan
| | - Chisato Mori
- Department of Sustainable Health Science, Chiba University Center for Preventive Medical Sciences, Chiba 263-8522, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Jianjun Yang
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
| | - Kenji Hashimoto
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
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Fang Z, Chen M, Qian J, Wang C, Zhang J. The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids. Cell Mol Neurobiol 2023; 43:543-559. [PMID: 35347532 PMCID: PMC11415173 DOI: 10.1007/s10571-022-01209-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 02/17/2022] [Indexed: 11/03/2022]
Abstract
Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.
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Affiliation(s)
- Zongwei Fang
- Department of Pharmacy, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, China
| | - Mingrong Chen
- Department of Pharmacy, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, China
| | - Jiafen Qian
- Department of Pharmacy, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, China
| | - Chunhua Wang
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, China.
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49
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Zhen J, Zhou Z, He M, Han HX, Lv EH, Wen PB, Liu X, Wang YT, Cai XC, Tian JQ, Zhang MY, Xiao L, Kang XX. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Front Endocrinol (Lausanne) 2023; 14:1085041. [PMID: 36824355 PMCID: PMC9941174 DOI: 10.3389/fendo.2023.1085041] [Citation(s) in RCA: 69] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/26/2023] [Indexed: 02/10/2023] Open
Abstract
Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.
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Affiliation(s)
- Jing Zhen
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
- School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, Jiangsu, China
| | - Zhou Zhou
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Meng He
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Hai-Xiang Han
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - En-Hui Lv
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Peng-Bo Wen
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xin Liu
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yan-Ting Wang
- Department of Biochemical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Xun-Chao Cai
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, China
| | - Jia-Qi Tian
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Meng-Ying Zhang
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Lei Xiao
- School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, Jiangsu, China
| | - Xing-Xing Kang
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
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50
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Salazar J, Morillo V, Suárez MK, Castro A, Ramírez P, Rojas M, Añez R, D’Marco L, Chacín-González M, Bermudez V. Role of Gut Microbiome in Atherosclerosis: Molecular and Therapeutic Aspects. Curr Cardiol Rev 2023; 19:e020223213408. [PMID: 36733248 PMCID: PMC10494273 DOI: 10.2174/1573403x19666230202164524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 12/07/2022] [Accepted: 12/07/2022] [Indexed: 02/04/2023] Open
Abstract
Atherosclerosis is one of the most relevant and prevalent cardiovascular diseases of our time. It is one of the pathological entities that increases the morbidity and mortality index in the adult population. Pathophysiological connections have been observed between atherosclerosis and the gut microbiome (GM), represented by a group of microorganisms that are present in the gut. These microorganisms are vital for metabolic homeostasis in humans. Recently, direct and indirect mechanisms through which GM can affect the development of atherosclerosis have been studied. This has led to research into the possible modulation of GM and metabolites as a new target in the prevention and treatment of atherosclerosis. The goal of this review is to analyze the physiopathological mechanisms linking GM and atherosclerosis that have been described so far. We also aim to summarize the recent studies that propose GM as a potential target in atherosclerosis management.
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Affiliation(s)
- Juan Salazar
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Valery Morillo
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - María K Suárez
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Ana Castro
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Paola Ramírez
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Milagros Rojas
- Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Roberto Añez
- Departamento de Endocrinología y Nutrición. Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Luis D’Marco
- Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, 46115, Spain
| | | | - Valmore Bermudez
- Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Colombia
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