Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

The term microbiome means not only a complex ecosystem of microbial species that colonize our body but also their genome and the surrounding environment in which they live. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age-related macular disorders. This review aims to underline the importance of the gut microbiome in relation to ocular health. After briefly introducing the characteristics of the gut microbiome in terms of composition and functions, the role of gut microbiome dysbiosis, in the development or progression of retinal diseases, is highlighted, focusing on the relationship between gut microbiome composition and retinal health based on the recently investigated gut-retina axis.

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Autophagy and Age-Related Eye Diseases

BioMed Research International ◽

10.1155/2019/5763658 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Xue Yang ◽

Xinan Pan ◽

Xiaorui Zhao ◽

Jin Luo ◽

Mingpu Xu ◽

...

Keyword(s):

Eye Diseases ◽

Regulatory Function ◽

Ocular Diseases ◽

Potential Therapeutic Target ◽

Age Related ◽

Different Types ◽

Survival And Development ◽

Catabolic Process

Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

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Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21031021 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1021 ◽

Cited By ~ 2

Author(s):

Carlota Suárez-Barrio ◽

Susana del Olmo-Aguado ◽

Eva García-Pérez ◽

María de la Fuente ◽

Francisco Muruzabal ◽

...

Keyword(s):

Ex Vivo ◽

Human Cell Line ◽

Antioxidant Effect ◽

Age Related Macular Degeneration ◽

Strong Impact ◽

Retinal Diseases ◽

Age Related ◽

Gene And Protein Expression

Oxidative stress has a strong impact on the development of retinal diseases such as age-related macular degeneration (AMD). Plasma rich in growth factors (PRGF) is a novel therapeutic approach in ophthalmological pathologies. The aim of this study was to analyze the antioxidant effect of PRGF in retinal epithelial cells (EPR) in in vitro and ex vivo retinal phototoxicity models. In vitro analyses were performed on ARPE19 human cell line. Viability and mitochondrial status were assessed in order to test the primary effects of PRGF. GSH level, and protein and gene expression of the main antioxidant pathway (Keap1, Nrf2, GCL, HO-1, and NQO1) were also studied. Ex vivo analyses were performed on rat RPE, and HO-1 and Nrf2 gene and protein expression were evaluated. The results show that PRGF reduces light insult by stimulating the cell response against oxidative damage and modulates the antioxidant pathway. We conclude that PRGF’s protective effect could prove useful as a new therapy for treating neurodegenerative disorders such as AMD.

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IMPACT OF PHYSICAL ACTIVITY OF PRESCHOOL CHILDREN ON THE DEVELOPMENT OF EXECUTIVE FUNCTIONS: THEORETICAL REVIEW OF STUDIES

Moscow University Psychology Bulletin ◽

10.11621/vsp.2020.03.10 ◽

2020 ◽

pp. 214-238

Author(s):

Alla A. Tvardovskaya ◽

Valerian F. Gabdulkhakov ◽

Natalya N. Novik ◽

Almira M. Garifullina

Keyword(s):

Physical Activity ◽

Preschool Children ◽

Research Problem ◽

Age Related ◽

Main Components ◽

Regulatory Functions ◽

Relationship Of ◽

The Relationship ◽

Positive Effect

Relevance. The increase of children interest in entertainment TV programs, mobile applications and video games available on the internet causes a significant decrease in their physical activity: children get used to a sedentary or lying down lifestyle. The research problem lies in the contradiction that arises due to understanding of the positive effect of physical activity on the development of the regulatory functions of a preschooler, and a significant decrease in this activity in the digital conditions of the modern educational environment. The relevance and prospects of the study of the relationship between regulatory functions and physical activity of preschool children in new digital environment are not yet fully realized. The objective of the paper is to review the studies by foreign scientists in order to identify and describe relevant indicators of physical activity in preschool children interrelated with the main components of regulatory functions (inhibitory control, working memory, cognitive flexibility). Method. A theoretical review of research papers published over the past ten years (2010–2020) on the subject of relationship of various physical activity indicators and regulatory functions in preschool children. Results. The paper provides a comparative analysis of studies conducted by foreign authors. It allows to reveal basic indicators of physical activity in children which are essential for the development of regulatory functions (sufficiency of physical activity; age-related appropriateness; the nature of physical activity; the form of physical activity arrangement), and particular indicators (the relationship of physical activity and regulatory functions in various sports, duration and intensity of physical activity, the availability of software for the development of physical activity in preschool children) as well. Conclusions. The review showed that the majority of the authors emphasized the significant role of basic physical activity indicators and their influence on regulatory functions. Aerobic exercises are the most effective in the development of regulatory functions in preschool children. Particular indicators are selected from the studies of the development of regulatory functions in specific sports (football, karate, yoga, mini-trampoline), and additional research on the duration and intensity of physical activity is needed.

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Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients

10.21203/rs.3.rs-50642/v2 ◽

2021 ◽

Author(s):

Xinyue Zhang ◽

Kun Guo ◽

Linjing Shi ◽

Ting Sun ◽

Songmei Geng

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

High Throughput Sequencing ◽

Interleukin 2 ◽

Negative Relationship ◽

Healthy Individuals ◽

Microbial Composition ◽

Microbiome Composition ◽

The Relationship

Abstract Background: Psoriasis is an inflammatory skin disease associated with multiple comorbidities and substantially diminishes patients’ quality of life. The gut microbiome has become a hot topic in psoriasis as it has been shown to affect both allergy and autoimmunity diseases in recent studies. Our objective was to identify differences in the fecal microbial composition of patients with psoriasis compared with healthy individuals to unravel the microbiota profiling in this autoimmune disease.Results: We collected fecal samples from 30 psoriasis patients and 30 healthy controls, sequenced them by 16S rRNA high-throughput sequencing, and identified the gut microbial composition using bioinformatic analyses including Quantitative Insights into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Our results showed that different relative abundance of certain bacterial taxa between psoriasis patients and healthy individuals, including Faecalibacterium and Megamonas, were increased in patients with psoriasis. It’s also implicated that many cytokines act as main effect molecules in the pathology of psoriasis. We selected the inflammation-related indicators that were abnormal in psoriasis patients and found the microbiome variations were associated with the level of them, especially interleukin-2 receptor showed a positive relationship with Phascolarctobacterium and a negative relationship with the dialister. The relative abundance of Phascolarctobacterium and dialister can be regard as predictors of psoriasis activity. The correlation analysis based on microbiota and Inflammation-related indicators showed that microbiota dysbiosis might induce an abnormal immune response in psoriasis. Conclusions: We concluded that the gut microbiome composition in psoriasis patients has been altered markedly and provides evidence to understand the relationship between gut microbiota and psoriasis. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of psoriasis and whether the relationship between gut microbiota and cytokines was involved.

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Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

10.7287/peerj.preprints.1754v1 ◽

2016 ◽

Author(s):

Melissa N. Conley ◽

Carmen P. Wong ◽

Kyle M. Duyck ◽

Norman Hord ◽

Emily Ho ◽

...

Keyword(s):

Immune System ◽

Murine Model ◽

Gut Microbiome ◽

Inflammatory Marker ◽

Low Grade ◽

Host Immune System ◽

Cancer Type ◽

Microbiome Composition ◽

Aged Mice ◽

Age Related

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.

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Synergistic Inhibitory Effect of the Gut Microbiome and Lithocholic Acid on Liver Fibrosis

10.21203/rs.3.rs-170652/v1 ◽

2021 ◽

Author(s):

Junwei Shao ◽

Tiantian Ge ◽

Senzhong Chen ◽

Zhi Chen

Keyword(s):

Liver Fibrosis ◽

Liver Function ◽

Gut Microbiome ◽

Lithocholic Acid ◽

Inhibitory Effect ◽

Tnf Α ◽

Cytokine Levels ◽

Serum Biochemical ◽

The Relationship

Abstract Background: Lithocholic acid are essential signaling molecules that mediate the relationship between the gut microbiome and liver function by regulating inflammation. The purpose of this study is to investigate the role of lithocholic acid in liver fibrosis. Methods: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of lithocholic acid, and the effects of lithocholic acid were evaluated by serum biochemical analysis and liver histology. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. Results: Lithocholic acid treatment increased the recruitment of NK cells and reduced the activation of NKT cells, and reduced M1 macrophages differentiation and increased M2 macrophages differentiation. Furthermore, the lithocholic acid prevented inflammatory liver disease by reducing TNF-α and IL-22 secretion. However, the effect of lithocholic acid disappeared when the host gut microbiome was treated with antibiotics. Conclusions: It showed that the activation of lithocholic acid-mediated signaling was linked to the inhibition of inflammation and improvement of liver fibrosis. The role of lithocholic acid in liver fibrosis is mediated by the gut microbiome. The association between the gut microbiome, lithocholic acid, and liver function can serve as a therapeutic target for liver fibrosis.

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The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review

Journal of Immunotherapy and Precision Oncology ◽

10.36401/jipo-21-10 ◽

2021 ◽

Author(s):

Ghada Araji ◽

Julian Maamari ◽

Fatima Ali Ahmad ◽

Rana Zareef ◽

Patrick Chaftari ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Therapeutic Interventions ◽

The Impact ◽

The Relationship ◽

Gut Microbiota Composition

ABSTRACT The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.

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Getting Old at the Top: The Role of Agentic and Communal Orientations in the Relationship Between Age and Follower Perceptions of Leadership Behaviors and Outcomes

Work Aging and Retirement ◽

10.1093/workar/waz012 ◽

2019 ◽

Vol 6 (1) ◽

pp. 46-58 ◽

Cited By ~ 1

Author(s):

Gregory R Thrasher ◽

Benjamin Biermeier-Hanson ◽

Marcus W Dickson

Keyword(s):

Leadership Behaviors ◽

Empirical Support ◽

Mediating Effect ◽

Socioemotional Selectivity ◽

Age Related ◽

Follower Perceptions ◽

Perceptions Of Leadership ◽

The Relationship ◽

Development Perspective

Abstract Leadership behaviors and the outcomes they foster have historically been central issues to organizational researchers and practitioners alike. Despite the continuing rise in the average age of the workforce, empirical research on leadership from a lifespan development perspective remains surprisingly rare. The current study applies socioemotional selectivity theory (SST) to address this gap in the literature in several ways. We test a holistic socioemotional model of age and leadership that examines dominance and amicability as agentic and communal mediators in the relationship between age and follower ratings of leadership behaviors and effectiveness. To accomplish this goal, we apply multisource data from a sample of 422 leaders with 2,016 follower ratings. We offer empirical support for a socioemotional model of age and leadership that highlights the role of communal shifts in the relationship between age and follower perceptions of leadership behaviors. Specifically, we find a positive mediating effect of amicability in the relationship between age and follower-rated relational-oriented leadership behaviors. Age also displayed a sequential mediating effect on effectiveness through amicability and relational-oriented leadership behaviors. Our results highlight the unique role that age-related changes in social orientations play in the perceptions of leadership behaviors and outcomes across the lifespan. Implications for research and practice are discussed.

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Human Skin, Oral, and Gut Microbiomes Predict Chronological Age

mSystems ◽

10.1128/msystems.00630-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Shi Huang ◽

Niina Haiminen ◽

Anna-Paola Carrieri ◽

Rebecca Hu ◽

Lingjing Jiang ◽

...

Keyword(s):

Gut Microbiome ◽

Prediction Models ◽

The Body ◽

Oral Microbiome ◽

Chronological Age ◽

Future Research ◽

Skin Microbiome ◽

Age Related ◽

Relative Value

ABSTRACT Human gut microbiomes are known to change with age, yet the relative value of human microbiomes across the body as predictors of age, and prediction robustness across populations is unknown. In this study, we tested the ability of the oral, gut, and skin (hand and forehead) microbiomes to predict age in adults using random forest regression on data combined from multiple publicly available studies, evaluating the models in each cohort individually. Intriguingly, the skin microbiome provides the best prediction of age (mean ± standard deviation, 3.8 ± 0.45 years, versus 4.5 ± 0.14 years for the oral microbiome and 11.5 ± 0.12 years for the gut microbiome). This also agrees with forensic studies showing that the skin microbiome predicts postmortem interval better than microbiomes from other body sites. Age prediction models constructed from the hand microbiome generalized to the forehead and vice versa, across cohorts, and results from the gut microbiome generalized across multiple cohorts (United States, United Kingdom, and China). Interestingly, taxa enriched in young individuals (18 to 30 years) tend to be more abundant and more prevalent than taxa enriched in elderly individuals (>60 yrs), suggesting a model in which physiological aging occurs concomitantly with the loss of key taxa over a lifetime, enabling potential microbiome-targeted therapeutic strategies to prevent aging. IMPORTANCE Considerable evidence suggests that the gut microbiome changes with age or even accelerates aging in adults. Whether the age-related changes in the gut microbiome are more or less prominent than those for other body sites and whether predictions can be made about a person’s age from a microbiome sample remain unknown. We therefore combined several large studies from different countries to determine which body site’s microbiome could most accurately predict age. We found that the skin was the best, on average yielding predictions within 4 years of chronological age. This study sets the stage for future research on the role of the microbiome in accelerating or decelerating the aging process and in the susceptibility for age-related diseases.

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Abstract 609: Plasma Carnitine is Associated with Gut Microbiome Composition, Diet, and Markers of Cardiometabolic Health

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.609 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Holly M Smith ◽

Muredach P Reilly ◽

Jane F Ferguson

Keyword(s):

Gut Microbiome ◽

Illumina Miseq ◽

Cardiometabolic Health ◽

Monounsaturated Fat ◽

Animal Products ◽

Microbiome Composition ◽

Processed Meats ◽

Plasma Carnitine ◽

Refined Carbohydrates ◽

The Relationship

Cardiometabolic health is influenced by both diet and gut microbiome composition, however mechanisms remain unclear. The dietary-derived metabolite carnitine has been of particular interest for its potential gut microbial-mediated relationship to atherosclerosis. Using plasma carnitine as an intermediate probe, we examined the relationship between diet, gut microbiome composition, circulating metabolite levels, and measurements of cardiometabolic health. Samples (blood, stool) and data (diet, anthropometrics) were collected from 136 healthy subjects. Purified stool 16S V4 DNA was sequenced (Illumina MiSeq, 300bp paired-end reads, ~150,000 reads/sample). Plasma carnitine was analyzed by mass spectrometry. There were several dietary components significantly associated with plasma carnitine, with an overall pattern of a diet rich in animal products and refined carbohydrates (dairy, processed meats, non-whole grains and starchy vegetables) associated with higher carnitine, while monounsaturated fat intake was associated with lower carnitine. Plasma carnitine was significantly negatively correlated with several bacterial genera including Blautia (r=-0.3 p=0.001), Parabacteroides (r=-0.2, p=0.03), and Coprococcus (r=-0.389, p<0.001). Carnitine levels above the median were associated with increases in cardiometabolic risk factors including higher systolic blood pressure (SBP, 118 vs 111 mmHg, p=0.014), BMI (27 vs. 24 kg/m 2 , p=0.002), waist-hip ratio (WHR, 0.85 vs 0.8, p=0.001) as well as higher levels of blood components associated with cardiovascular risk, including circulating monocytes (p=0.007) and hemoglobin (p=0.006). Both diet and microbiome composition also associated with several risk markers (WHR, SBP, hemoglobin), albeit to a lesser extent than plasma carnitine. In conclusion, we provide evidence for inter-related relationships between diet, microbiome composition, circulating metabolites, and markers of cardiometabolic health.

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