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Lv H, Wang Z, Huang C, Yu X, Li X, Song X. Causal Links between Gut Microbiota, Blood Metabolites, Immune Cells, Inflammatory Proteins, and Myopia: A Mendelian Randomization Study. OPHTHALMOLOGY SCIENCE 2025; 5:100684. [PMID: 40206264 PMCID: PMC11979374 DOI: 10.1016/j.xops.2024.100684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 11/27/2024] [Accepted: 12/13/2024] [Indexed: 04/11/2025]
Abstract
Purpose This study aimed to investigate causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia through Mendelian randomization (MR) analysis. Design Mendelian randomization study. Subjects Genome-wide association study (GWAS) data of 412 gut microbiota, 1400 blood metabolites/metabolite ratios, 731 immune cell traits, and 91 circulating inflammatory proteins from the public GWAS database. Genome-wide association study data of myopia from the public GWAS database and FinnGen consortium. Methods Two-sample MR analysis and meta-analysis were employed using 4 methods, with inverse-variance weighted as the primary approach, to investigate potential causal links. Metabolic pathway analysis was conducted to explore metabolic pathways. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO were used for sensitivity analyses. Mediation and reverse MR analyses were also carried out to identify potential mediation relationships and modification effects of myopia. Main Outcome Measures Causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia. Results We identified causal effects of 34 and 22 gut microbiota/bacterial pathways, 131 and 98 blood metabolites/metabolite ratios, 60 and 37 immune cell traits, and 5 and 2 circulating inflammatory proteins on myopia (ukb-b-6353 and R10_H7_MYOPIA, respectively). Overlapping causal relationships were found for 1 gut bacterial pathway, 10 blood metabolites/metabolite ratios, and 2 immune cell traits across both outcomes; however, none of these overlaps reached significance after meta-analysis. The Small Molecule Pathway Database and Kyoto Encyclopedia of Genes and Genomes database enriched 14 significant pathways. Flavin adenine dinucleotide was involved in 8 pathways in both databases. Furthermore, the causal effect of glycochenodeoxycholate glucuronide on myopia was mediated by acetyl-CoA fermentation to butanoate lI, with mediation proportion of 19.03% (ukb-b-6353) and 19.48% (R10_H7_MYOPIA). Reverse MR analysis identified modification effects of myopia (ukb-b-6353) on gut microbiota, blood metabolites, and circulating inflammatory proteins. Conclusions These findings demonstrated significant causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia. Gut microbiota pathway may mediate the causal effects of blood metabolite on myopia. This may provide researchers with a new perspective in exploring the biological mechanisms of myopia and may lead to the exploration of earlier treatment strategies. Financial Disclosures The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Affiliation(s)
- Huibin Lv
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
| | - Zhenyu Wang
- Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chen Huang
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China
| | - Xiaotong Yu
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China
| | - Xuemin Li
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
| | - Xudong Song
- Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Berzack S, Galor A. Microbiome-based therapeutics for ocular diseases. Clin Exp Optom 2025; 108:115-122. [PMID: 39617011 PMCID: PMC11875938 DOI: 10.1080/08164622.2024.2422479] [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: 09/16/2024] [Revised: 10/22/2024] [Accepted: 10/23/2024] [Indexed: 12/08/2024] Open
Abstract
The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.
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Affiliation(s)
- Shannan Berzack
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA
| | - Anat Galor
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
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Trojacka E, Izdebska J, Szaflik J, Przybek-Skrzypecka J. The Ocular Microbiome: Micro-Steps Towards Macro-Shift in Targeted Treatment? A Comprehensive Review. Microorganisms 2024; 12:2232. [PMID: 39597621 PMCID: PMC11596073 DOI: 10.3390/microorganisms12112232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/14/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024] Open
Abstract
A healthy ocular surface is inhabited by microorganisms that constitute the ocular microbiome. The core of the ocular microbiome is still a subject of debate. Numerous culture-dependent and gene sequencing studies have revealed the composition of the ocular microbiome. There was a confirmed correlation between the ocular microbiome and ocular surface homeostasis as well as between ocular dysbiosis and pathologies such as blepharitis, microbial keratitis, and conjunctivitis. However, the role of the ocular microbiome in the pathogenesis and treatment of ocular surface diseases remains unclear. This article reviews available data on the ocular microbiome and microbiota, their role in maintaining ocular homeostasis, and the impact of dysbiosis on several ophthalmic disorders. Moreover, we aimed to discuss potential treatment targets within the ocular microbiota.
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Affiliation(s)
- Ewelina Trojacka
- SPKSO Ophthalmic University Hospital in Warsaw, 03-709 Warsaw, Poland; (E.T.); (J.I.); (J.S.)
| | - Justyna Izdebska
- SPKSO Ophthalmic University Hospital in Warsaw, 03-709 Warsaw, Poland; (E.T.); (J.I.); (J.S.)
- Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland
| | - Jacek Szaflik
- SPKSO Ophthalmic University Hospital in Warsaw, 03-709 Warsaw, Poland; (E.T.); (J.I.); (J.S.)
- Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland
| | - J. Przybek-Skrzypecka
- SPKSO Ophthalmic University Hospital in Warsaw, 03-709 Warsaw, Poland; (E.T.); (J.I.); (J.S.)
- Department of Ophthalmology, Medical University of Warsaw, 03-709 Warsaw, Poland
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Ullah Z, Tao Y, Mehmood A, Huang J. The Role of Gut Microbiota in the Pathogenesis of Glaucoma: Evidence from Bibliometric Analysis and Comprehensive Review. Bioengineering (Basel) 2024; 11:1063. [PMID: 39593723 PMCID: PMC11591249 DOI: 10.3390/bioengineering11111063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/08/2024] [Accepted: 10/19/2024] [Indexed: 11/28/2024] Open
Abstract
The relationship between gut microbiota and glaucoma has garnered significant interest, with emerging evidence suggesting that gut dysbiosis, inflammation, and immune mechanisms may contribute to glaucoma pathogenesis. Understanding these interactions through the gut-retina axis offers new insights into disease progression and potential therapeutic options. This study combines bibliometric analysis and literature review to evaluate research trends and key research areas related to gut microbiota's role in glaucoma. Our data were collected from the Web of Science Core Collection (WoSCC) and included the English original articles and reviews published between 1 January 2008, and 6 August 2024. Visual and statistical analyses were conducted using VOSviewer and CiteSpace. The analyses comprised 810 citations from leading journals, representing contributions from 23 countries/regions, 111 institutions, 40 journals, and 321 authors. Among the countries and regions involved, the USA and China were the leading contributors, publishing the most articles and being major research hubs. The Experimental Eye Research and Investigative Ophthalmology & Visual Science were the top journals in citation and co-citations that produced high-quality publications. The top 10 highly cited articles were published in high-ranking, top-quartile journals. The frequently occurring keywords were "glaucoma", "microbiota", "gut microbiota", "inflammation", "gut-retina axis", and "probiotics". Our study highlights the growing interest in the association between gut microbiota and glaucoma. It summarizes the possible ways gut microbiota dysbiosis, systemic and neuroinflammation, and autoimmune mechanisms contribute to glaucomatous pathogenesis. Future research should focus on mechanistic studies to elucidate the pathways linking gut microbiota to glaucoma development and progression.
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Affiliation(s)
- Zakir Ullah
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410017, China; (Z.U.); (Y.T.)
- Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei 115014, Taiwan
| | - Yuanyuan Tao
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410017, China; (Z.U.); (Y.T.)
| | - Amina Mehmood
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan;
| | - Jufang Huang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410017, China; (Z.U.); (Y.T.)
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Kammoun S, Rekik M, Dlensi A, Aloulou S, Smaoui W, Sellami S, Trigui K, Gargouri R, Chaari I, Sellami H, Elatoui D, Khemakhem N, Hadrich I, Neji S, Abdelmoula B, Bouayed Abdelmoula N. The gut-eye axis: the retinal/ocular degenerative diseases and the emergent therapeutic strategies. Front Cell Neurosci 2024; 18:1468187. [PMID: 39391760 PMCID: PMC11464360 DOI: 10.3389/fncel.2024.1468187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
The interplay between human microbiota and various physiological systems has garnered significant attention in recent years. The gut microbiota plays a critical role in maintaining physiological homeostasis and influences various aspects of human health, particularly via the gut brain axis. Since 2017, the challenging concept of the gut-retina axis has emerged thanks to a network analysis emphasizing the potential role of the gut microbiota disruption in the development of the age-related macular degeneration and further retinal damages. Many other ocular disorders have been linked to the dysbiosis of the gut microbiota, including uveitis and glaucoma. It has been shown that age related macular degeneration can be prevented or reversed using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as others types of microbiota such as the ocular surface microbiota and the development/progression of age related as well as inherited retinal degenerations and other degenerative eye diseases, has recently been broadened. Therefore, the pathogenesis of several eye diseases has recently been associated with a larger perception called the gut eye axis. This mini-review examines the potential mechanisms underlying the gut eye axis and suggests implications for the management of eye diseases. By understanding the modulation of the gut microbiota and its impact on eye disease, this mini-review provides insight into potential therapeutic interventions and avenues for future research.
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Affiliation(s)
- Sonda Kammoun
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
- Ophthalmology Department, Faculty of Medicine, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
| | - Mona Rekik
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
- Ophthalmology Department, Faculty of Medicine, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
| | - Aryj Dlensi
- Ophthalmology Department, Faculty of Medicine, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
| | - Samir Aloulou
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
- Medical Carcinology Department, Faculty of Medicine, Mohamed Ben Sassi University Hospital of Gabes, University of Sfax, Sfax, Tunisia
| | - Walid Smaoui
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
- Urology Department, Faculty of Medicine, Habib Bourguiba University Hospital, University of Sfax, Sfax, Tunisia
| | - Sahla Sellami
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
| | - Khaled Trigui
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
| | - Rahma Gargouri
- Drosophila Research Unit UR22ES03 FMS, University of Sfax, Sfax, Tunisia
| | - Imen Chaari
- Drosophila Research Unit UR22ES03 FMS, University of Sfax, Sfax, Tunisia
| | - Hayet Sellami
- Drosophila Research Unit UR22ES03 FMS, University of Sfax, Sfax, Tunisia
- Parasitology and Mycology Department, Faculty of Medicine, University of Sfax, Sfax, Tunisia
| | - Dhawia Elatoui
- Drosophila Research Unit UR22ES03 FMS, University of Sfax, Sfax, Tunisia
| | - Nahed Khemakhem
- Fungal and Parasitic Molecular Biology Laboratory LR05ES11 FMS, University of Sfax, Sfax, Tunisia
| | - Ines Hadrich
- Fungal and Parasitic Molecular Biology Laboratory LR05ES11 FMS, University of Sfax, Sfax, Tunisia
| | - Sourour Neji
- Parasitology and Mycology Department, Faculty of Medicine, University of Sfax, Sfax, Tunisia
- Fungal and Parasitic Molecular Biology Laboratory LR05ES11 FMS, University of Sfax, Sfax, Tunisia
| | - Balkiss Abdelmoula
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
| | - Nouha Bouayed Abdelmoula
- Genomics of Signalopathies at the Service of Precision Medicine LR23ES07 FMS, University of Sfax, Sfax, Tunisia
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Haghshenas L, Banihashemi S, Malekzadegan Y, Catanzaro R, Moghadam Ahmadi A, Marotta F. Microbiome as an endocrine organ and its relationship with eye diseases: Effective factors and new targeted approaches. World J Gastrointest Pathophysiol 2024; 15:96446. [PMID: 39355345 PMCID: PMC11440246 DOI: 10.4291/wjgp.v15.i5.96446] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 09/04/2024] [Accepted: 09/13/2024] [Indexed: 09/20/2024] Open
Abstract
Microbiome is an endocrine organ that refers to both the complicated biological system of microbial species that colonize our bodies and their genomes and surroundings. Recent studies confirm the connection between the microbiome and eye diseases, which are involved in the pathogenesis of eye diseases, including age-related macular disorders, diabetic retinopathy, glaucoma, retinitis pigmentosa, dry eye, and uveitis. The aim of this review is to investigate the microbiome in relation to eye health. First, a brief introduction of the characteristics of the gut microorganisms terms of composition and work, the role of dysbiosis, the gut microbiome and the eye microbiome in the progression of eye illnesses are highlighted, then the relationship among the microbiome and the function of the immune system and eye diseases, the role of inflammation and aging and the immune system, It has been reviewed and finally, the control and treatment goals of microbiome and eye diseases, the role of food factors and supplements, biotherapy and antibiotics in relation to microbiome and eye health have been reviewed.
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Affiliation(s)
- Leila Haghshenas
- Department of Clinical Bioinformatics, Harvard Medical School, Boston, MA 02115, United States
| | - Sara Banihashemi
- Department of Bioscience, School of Science and Technology, Nottingham Trend University, Nottingham NG1 4FQ, United Kingdom
| | - Yalda Malekzadegan
- Department of Microbiology, Saveh University of Medical Sciences, Saveh 3919676651, Iran
| | - Roberto Catanzaro
- Department of Clinical and Experimental Medicine, University of Catania, Catania 95123, Catania, Italy
| | - Amir Moghadam Ahmadi
- Department of Neuroimmunology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
| | - Francesco Marotta
- Department of Human Nutrition and Food Sciences, Texas Women University, Milano 20154, Italy
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Tîrziu AT, Susan M, Susan R, Sonia T, Harich OO, Tudora A, Varga NI, Tiberiu-Liviu D, Avram CR, Boru C, Munteanu M, Horhat FG. From Gut to Eye: Exploring the Role of Microbiome Imbalance in Ocular Diseases. J Clin Med 2024; 13:5611. [PMID: 39337098 PMCID: PMC11432523 DOI: 10.3390/jcm13185611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/16/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Background: The gut microbiome plays a crucial role in human health, and recent research has highlighted its potential impact on ocular health through the gut-eye axis. Dysbiosis, or an imbalance in the gut microbiota, has been implicated in various ocular diseases. Methods: A comprehensive literature search was conducted using relevant keywords in major electronic databases, prioritizing recent peer-reviewed articles published in English. Results: The gut microbiota influences ocular health through immune modulation, maintenance of the blood-retinal barrier, and production of beneficial metabolites. Dysbiosis can disrupt these mechanisms, contributing to ocular inflammation, tissue damage, and disease progression in conditions such as uveitis, age-related macular degeneration, diabetic retinopathy, dry eye disease, and glaucoma. Therapeutic modulation of the gut microbiome through probiotics, prebiotics, synbiotics, and fecal microbiota transplantation shows promise in preclinical and preliminary human studies. Conclusions: The gut-eye axis represents a dynamic and complex interplay between the gut microbiome and ocular health. Targeting the gut microbiome through innovative therapeutic strategies holds potential for improving the prevention and management of various ocular diseases.
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Affiliation(s)
- Andreea-Talida Tîrziu
- Department of General Medicine, Doctoral School, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Department of Ophthalmology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Monica Susan
- Centre for Preventive Medicine, Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
| | - Razvan Susan
- Centre for Preventive Medicine, Department of Family Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
| | - Tanasescu Sonia
- Department of Pediatrics, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
| | - Octavia Oana Harich
- Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
| | - Adelina Tudora
- Multidisciplinary Doctoral School, Vasile Goldis Western University of Arad, Strada Liviu Rebreanu 86, 310419 Arad, Romania
| | - Norberth-Istvan Varga
- Department of General Medicine, Doctoral School, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Dragomir Tiberiu-Liviu
- Medical Semiology II Discipline, Internal Medicine Department, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Cecilia Roberta Avram
- Department of Residential Training and Post-University Courses, "Vasile Goldis" Western University, 310414 Arad, Romania
| | - Casiana Boru
- Department of Medicine, "Vasile Goldis" University of Medicine and Pharmacy, 310414 Arad, Romania
| | - Mihnea Munteanu
- Department of Ophthalmology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Florin George Horhat
- Multidisciplinary Research Center on Antimicrobial Resistance (MULTI-REZ), Microbiology Department, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
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Krilis M, Fry L, Ngo P, Goldberg I. The gut microbiome and primary open angle glaucoma: Evidence for a 'gut-glaucoma' axis? Eur J Ophthalmol 2024; 34:924-930. [PMID: 38086752 DOI: 10.1177/11206721231219147] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Glaucoma presents an epidemiological burden as the leading cause of irreversible blindness globally and the most common cause of preventable blindness. While elevated intraocular pressure is the strongest modifiable risk factor, the exact mechanisms of retinal ganglion cell damage leading to progressive vision loss are not entirely understood. Studies of other neurodegenerative diseases show a potential for human gut microbiome dysbiosis to play a pathogenic role. An investigation into whether the microbiome, a potential modifiable risk factor, has significance in glaucoma enables exploration of prophylactic or additive treatments. Elevated population levels of specific bacterial species have been noted in glaucoma patients, particularly Prevotellaceae, Enterobacteriaceae and Escherichia coli, while Megomonas is speculated to be protective. Evidence also points to systemic neuro-inflammation and disruption of autoimmune processes as a result of imbalances in both human and animal models, where heat shock proteins may contribute to pathogenesis. Further research into the influence of gut microbiome on pathogenesis offers a chance to minimise irreversible vision loss in glaucoma.
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Affiliation(s)
- Matthew Krilis
- Oxford Eye Hospital, Oxford, UK
- Save Sight Institute, Sydney, Australia
| | - Lewis Fry
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Patrick Ngo
- School of Medicine, University of Sydney, Camperdown, Australia
| | - Ivan Goldberg
- Discipline of Ophthalmology, University of Sydney, Sydney, Australia
- Glaucoma Unit, Sydney Eye Hospital, Sydney, Australia
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Huang L, Hong Y, Fu X, Tan H, Chen Y, Wang Y, Chen D. The role of the microbiota in glaucoma. Mol Aspects Med 2023; 94:101221. [PMID: 37866106 DOI: 10.1016/j.mam.2023.101221] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/24/2023]
Abstract
Glaucoma is a common irreversible vision loss disorder because of the gradual loss of retinal ganglion cells (RGCs) and the optic nerve axons. Major risk factors include elder age and high intraocular pressure (IOP). However, high IOP is neither necessary nor sufficient to cause glaucoma. Some non-IOP signaling cascades can mediate RGC degeneration. In addition, gender, diet, obesity, depression, or anxiety also contribute to the development of glaucoma. Understanding the mechanism of glaucoma development is crucial for timely diagnosis and establishing new strategies to improve current IOP-reducing therapies. The microbiota exerts a marked influence on the human body during homeostasis and disease. Many glaucoma patients have abnormal compositions of the microbiota (dysbiosis) in multiple locations, including the ocular surface, intraocular cavity, oral cavity, stomach, and gut. Here, we discuss findings in the last ten years or more about the microbiota and metabolite changes in animal models, patients with three risk factors (aging, obesity, and depression), and glaucoma patients. Antigenic mimicry and heat stress protein (HSP)-specific T-cell infiltration in the retina may be responsible for commensal microbes contributing to glaucomatous RGC damage. LPS-TLR4 pathway may be the primary mechanism of oral and ocular surface dysbiosis affecting glaucoma. Microbe-derived metabolites may also affect glaucoma pathogenesis. Homocysteine accumulation, inflammatory factor release, and direct dissemination may link gastric H. pylori infection and anterior chamber viral infection (such as cytomegalovirus) to glaucoma. Potential therapeutic protocols targeting microbiota include antibiotics, modified diet, and stool transplant. Later investigations will uncover the underlying molecular mechanism connecting dysbiosis to glaucoma and its clinical applications in glaucoma management.
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Affiliation(s)
- Ling Huang
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yiwen Hong
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiangyu Fu
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Haishan Tan
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yongjiang Chen
- The School of Optometry and Vision Science, University of Waterloo, 200 University Ave. W., Waterloo, ON, N2L 3G1, Canada
| | - Yujiao Wang
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Danian Chen
- The Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China; The Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Janetos TM, Zakaria N, Goldstein DA. The Microbiome and Uveitis: A Narrative Review. THE AMERICAN JOURNAL OF PATHOLOGY 2023; 193:1638-1647. [PMID: 37024044 DOI: 10.1016/j.ajpath.2023.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 03/11/2023] [Accepted: 03/22/2023] [Indexed: 04/07/2023]
Abstract
The human intestinal microbiome is composed of hundreds of species and has recently been recognized as an important source of immune homeostasis. While dysbiosis, an altered microbiome from the normal core microbiome, has been associated with both intestinal and extraintestinal autoimmune disorders, including uveitis, causality has been difficult to establish. There are four proposed mechanisms of how the gut microbiome may influence the development of uveitis: molecular mimicry, imbalance of regulatory and effector T cells, increased intestinal permeability, and loss of intestinal metabolites. This review summarizes current literature on both animal and human studies that establish the link between dysbiosis and the development of uveitis, as well as provides evidence for the above mechanisms. Current studies provide valuable mechanistic insights as well as identify potential therapeutic targets. However, study limitations and the wide variability in the intestinal microbiome among populations and diseases make a specific targeted therapy difficult to establish. Further longitudinal clinical studies are required to identify any potential therapeutic that targets the intestinal microbiome.
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Affiliation(s)
- Timothy M Janetos
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
| | - Nancy Zakaria
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Arab Republic of Egypt
| | - Debra A Goldstein
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Chen S, Wang N, Xiong S, Xia X. The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine. EPMA J 2023; 14:539-552. [PMID: 37605653 PMCID: PMC10439875 DOI: 10.1007/s13167-023-00336-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/29/2023] [Indexed: 08/23/2023]
Abstract
Background Glaucoma is the leading cause of irreversible blindness worldwide. Emerged evidence has shown that glaucoma is considered an immune system related disorder. The gut is the largest immune organ in the human body and the gut microbiota (GM) plays an irreversible role in maintaining immune homeostasis. But, how the GM influences glaucoma remains unrevealed. This study aimed at investigating the key molecules/pathways mediating the GM and the glaucoma to provide new biomarkers for future predictive, preventive, and personalized medicine. Methods Datasets from the primary open-angle glaucoma (POAG) patients (GSE138125) and datasets for target genes of GM/GM metabolites were downloaded from a public database. For GSE138125, the differentially expressed genes (DEGs) between healthy and POAG samples were identified. And the online Venn diagram tool was used to obtain the DEGs from POAG related to GM. After which GM-related DEGs were analyzed by correlation analysis, pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Human trabecular meshwork cells were used for validation, and the mRNA level of hub genes was verified by quantitative real-time polymerase chain reaction (RT-qPCR) in the in vitro glaucoma model. Results A total of 16 GM-related DEGs in POAG were identified from the above 2 datasets (9 upregulated genes and 7 downregulated genes). Pathway enrichment analysis indicated that these genes are mostly enriched in immune regulation especially macrophages-related pathways. Then 6 hub genes were identified by PPI network analysis and construction of key modules. Finally, RT-qPCR confirmed that the expression of the hub genes in the in vitro glaucoma model was consistent with the results of bioinformatics analysis of the mRNA chip. Conclusion This bioinformatic study elucidates NFKB1, IL18, KITLG, TLR9, FKBP2, and HDAC4 as hub genes for POAG and GM regulation. Immune response modulated by macrophages plays an important role in POAG and may be potential targets for future predictive, preventive, and personalized diagnosis and treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-023-00336-2.
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Affiliation(s)
- Si Chen
- Eye Center of Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
- Hunan Key Laboratory of Ophthalmology, Changsha, Hunan China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan China
| | - Nan Wang
- Eye Center of Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
- Hunan Key Laboratory of Ophthalmology, Changsha, Hunan China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan China
| | - Siqi Xiong
- Eye Center of Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
- Hunan Key Laboratory of Ophthalmology, Changsha, Hunan China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan China
| | - Xiaobo Xia
- Eye Center of Xiangya Hospital, Central South University, Changsha, 410008 Hunan China
- Hunan Key Laboratory of Ophthalmology, Changsha, Hunan China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan China
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12
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Campagnoli LIM, Varesi A, Barbieri A, Marchesi N, Pascale A. Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases. Int J Mol Sci 2023; 24:13338. [PMID: 37686143 PMCID: PMC10488056 DOI: 10.3390/ijms241713338] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/20/2023] [Accepted: 08/26/2023] [Indexed: 09/10/2023] Open
Abstract
The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.
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Affiliation(s)
| | - Angelica Varesi
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy;
| | - Annalisa Barbieri
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
| | - Nicoletta Marchesi
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
| | - Alessia Pascale
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
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13
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Tang Y, Shah S, Cho KS, Sun X, Chen DF. Metabolomics in Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis. Front Neurosci 2022; 16:835736. [PMID: 35645711 PMCID: PMC9135181 DOI: 10.3389/fnins.2022.835736] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/15/2022] [Indexed: 01/01/2023] Open
Abstract
Glaucoma is a leading cause of blindness worldwide. It is suggested that primary open angle glaucoma (POAG), the most common form of glaucoma, may be associated with significant metabolic alternations, but the systemic literature review and meta-analysis in the area have been missing. Altered metabolomic profiles in the aqueous humor and plasma may serve as possible biomarkers for early detection or treatment targets. In this article, we performed a systematic meta-analysis of the current literature surrounding the metabolomics of patients with POAG and metabolites associated with the disease. Results suggest several metabolites found to be specifically altered in patients with POAG, suggesting broad generalizability and pathways for future research.
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Affiliation(s)
- Yizhen Tang
- Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - Simran Shah
- Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - Kin-Sang Cho
- Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
| | - Xinghuai Sun
- Department of Ophthalmology, Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Dong Feng Chen
- Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States
- *Correspondence: Dong Feng Chen,
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14
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Mucosal immunology of the ocular surface. Mucosal Immunol 2022; 15:1143-1157. [PMID: 36002743 PMCID: PMC9400566 DOI: 10.1038/s41385-022-00551-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 05/26/2022] [Accepted: 06/10/2022] [Indexed: 02/04/2023]
Abstract
The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories. Dry eye, a dysfunction of the lacrimal glands and/or Meibomian glands, which can both cause, or arise from, sensory defects, including those caused by corneal herpes virus infection, serve as examples of these perturbations and will be discussed ahead. To preserve vision, dense neuronal and immune networks sense various stimuli and orchestrate responses, which must be tightly controlled to provide protection, while simultaneously minimizing collateral damage. All this happens against the backdrop of, and can be modified by, the microorganisms that colonize the ocular mucosa long term, or that are simply transient passengers introduced from the environment. This review will attempt to synthesize the existing knowledge and develop trends in the study of the unique mucosal and immune elements of the ocular surface.
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15
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Bringer MA, Gabrielle PH, Bron AM, Creuzot-Garcher C, Acar N. The gut microbiota in retinal diseases. Exp Eye Res 2021; 214:108867. [PMID: 34856206 DOI: 10.1016/j.exer.2021.108867] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/25/2021] [Accepted: 11/23/2021] [Indexed: 02/06/2023]
Abstract
The gut microbiota is a complex ecosystem that inhabits the gastrointestinal tract and consists of archaea, fungi, viruses, and bacteria, with bacteria being dominant. From birth onwards, it coevolves dynamically together with the host. The composition of the gut microbiota is under the influence of a complex interplay between both host and environmental factors. Scientific advances in the past few decades have shown that it is essential in maintaining homeostasis and tipping the balance between health and disease. In addition to its role in food digestion, the gut microbiota is implicated in regulating multiple physiological processes in the host gut mucosa and in distant organs such as the brain. Persistent imbalance between gut microbial communities, termed "dysbiosis," has been associated with several inflammatory and metabolic diseases as well as with central nervous system disorders. In this review, we present the state of the art of current knowledge on an emerging concept, the microbiota-retina axis, and the potential role of its disturbance in the development of retinopathies. We also describe several microbiota-targeting strategies that could constitute preventive and therapeutic tools for retinopathies.
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Affiliation(s)
- Marie-Agnès Bringer
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France.
| | - Pierre-Henry Gabrielle
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France; Ophthalmology Department, University Hospital, F-21000, Dijon, France
| | - Alain M Bron
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France; Ophthalmology Department, University Hospital, F-21000, Dijon, France
| | - Catherine Creuzot-Garcher
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France; Ophthalmology Department, University Hospital, F-21000, Dijon, France
| | - Niyazi Acar
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, F-21000, Dijon, France
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Xue W, Li JJ, Zou Y, Zou B, Wei L. Microbiota and Ocular Diseases. Front Cell Infect Microbiol 2021; 11:759333. [PMID: 34746029 PMCID: PMC8566696 DOI: 10.3389/fcimb.2021.759333] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/06/2021] [Indexed: 12/12/2022] Open
Abstract
Recent advances have identified significant associations between the composition and function of the gut microbiota and various disorders in organ systems other than the digestive tract. Utilizing next-generation sequencing and multiomics approaches, the microbial community that possibly impacts ocular disease has been identified. This review provides an overview of the literature on approaches to microbiota analysis and the roles of commensal microbes in ophthalmic diseases, including autoimmune uveitis, age-related macular degeneration, glaucoma, and other ocular disorders. In addition, this review discusses the hypothesis of the "gut-eye axis" and evaluates the therapeutic potential of targeting commensal microbiota to alleviate ocular inflammation.
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Affiliation(s)
- Wei Xue
- State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
| | - Jing Jing Li
- State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
| | - Yanli Zou
- State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China.,Department of Ophthalmology, Affiliated Foshan Hospital, Southern Medical University, Foshan, China
| | - Bin Zou
- State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
| | - Lai Wei
- State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China
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Trimethylamine N-Oxide, a Gut Microbiota-Derived Metabolite, Is Associated with Cardiovascular Risk in Psoriasis: A Cross-Sectional Pilot Study. Dermatol Ther (Heidelb) 2021; 11:1277-1289. [PMID: 33983475 PMCID: PMC8322249 DOI: 10.1007/s13555-021-00547-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 04/30/2021] [Indexed: 02/07/2023] Open
Abstract
Introduction Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is involved in the pathogenesis of atherosclerosis and cardiovascular diseases. Psoriasis is associated with increased cardiovascular risk that is not captured by traditional biomarkers. The aim of the present study was to assess TMAO concentration in psoriasis and evaluate the relationship between TMAO and cardiovascular risk in psoriatic patients. Methods In 72 patients with psoriasis and 40 age- and sex-matched non-psoriatic controls, we evaluated fasting plasma TMAO, measured by high-performance liquid chromatography, and cardiovascular risk assessed by various scoring systems such as Framingham, QRISK2, AHA/ACC, and Reynolds risk scores. Results In patients with psoriasis, TMAO concentration was significantly higher than in the control group (195.68 [133.54–332.58] ng/ml versus 126.06 [84.29–156.88] ng/ml, respectively; p < 0.001). Plasma TMAO concentration was significantly correlated with age, total cholesterol, triglycerides, systolic and diastolic blood pressure. Furthermore, the receiver-operating characteristic (ROC) and multiple regression analysis showed that TMAO is an independent predictor of cardiovascular risk. Conclusion TMAO is a valuable candidate for biomarker and a translational link between dysbiosis and atherosclerosis in psoriasis.
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