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1.
Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action.
Naja, F, Hamadeh, R
European journal of clinical nutrition. 2020;74(8):1117-1121
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This Lebanese articled provides a commentary on the evolving COVID-19 pandemic and aims to give a framework for Nutritional action to help the physical and mental health of individuals, communities, and nations. At an individual level the focus is on the link between diet and immunity and the profound effect diet has on people’s immune system and disease susceptibility. An adequate intake of iron, zinc, and vitamins A, E, B6, and B12 is predominantly vital for the maintenance of immune function. Individuals should aim to eat as healthily as possible, including a wide range of fruits and vegetables, limit snacking, take regular exercise and get an adequate amount of sleep to support their health. Single foods promising cures or prevention of infection are unfounded claims which can give a false sense of security. The focus for communities is on food availability, for nations its food security and on a global level it is about food trade agreements. Its important to protect against hoarding and panic buying to ensure enough food for everyone. National economic instability during COVID-19 can lead to a risk of food security so governments are advised to support local agricultural produce and reduce their reliance on imported goods. Global supply chains and agreements need to be respected to lessen the impact further down the supply chain. The health of each individual has a direct impact on the community and nation and is a direct consequence of their dietary awareness and choices.
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Gut microbial metabolites in depression: understanding the biochemical mechanisms.
Caspani, G, Kennedy, S, Foster, JA, Swann, J
Microbial cell (Graz, Austria). 2019;6(10):454-481
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Major depressive disorder is a leading cause of disability and is linked to shortened life expectancy and suicide. Despite its prevalence, for near to a third of patients, long-term treatment options are ineffective. In addition to the primary presentation of persistent low mood, other emotional and physiological symptoms, researchers have also identified alterations in metabolism, hormones and the immune system. Furthermore, increasing evidence suggests that depression and depressive behaviour is also influenced by divergences in gut health and gut bacteria composition. With insights from animal and human research, this review highlights how the gut and gut bacteria-derived metabolites can directly or indirectly influence mood. Described are the pathways of how the gut and its microorganism communicate with the brain, the essential role the immune system has as part of the gut-brain communication, and the impact of low-grade, chronic inflammation on neurofunction. Comprehensive summaries are dedicated to how several metabolites or by-products from gut bacteria can influence the nervous system and gene expression in relation to depression. These include substances like neurotransmitters, short-chain fatty acids, tryptophan metabolites, lactate, bile acids, choline metabolites and folate. This article yields a detailed overview of how gut health and microbiota can influence neurofunction and mental health. The authors promote the idea of the gut as a suitable target for the management of depressive disorders, whilst also eluding to the current limitations and need for further research.
Abstract
Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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Food Allergies and Ageing.
De Martinis, M, Sirufo, MM, Viscido, A, Ginaldi, L
International journal of molecular sciences. 2019;20(22)
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Food allergies are thought to affect 200 million people worldwide and are most prevalent in children. However, food allergies are also becoming more frequent in the elderly. The authors discuss details of several underlying mechanisms of food allergies in the elderly: 1) Immunosensecence, that is an age-related remodelling of the immune system which favours the development of food allergies. 2) Age related effects on local immune responses, especially on the gastrointestinal mucosa with regards to mucosal tolerance (i.e. tolerance to food allergens). 3) In the elderly, the integrity of the gut epithelial barrier is compromised which contributes to chronic inflammation and allows allergens to penetrate into tissues where they can trigger an immune response. The elderly also commonly have decreased digestive secretions, which leads to proteins not being fully broken down, an additional risk factor for food allergies. 4) Age associated alterations of the gut microbiota may favour the development of food allergies in a number of ways. 5) Nutrient deficiencies, which are common in the elderly, also contribute to the development of food allergies through several mechanisms.
Abstract
All over the world, there is an increase in the overall survival of the population and the number of elderly people. The incidence of allergic reactions is also rising worldwide. Until recently, allergies, and in particular food allergies (FAs), was regarded as a pediatric problem, since some of them start in early childhood and may spontaneously disappear in adulthood. It is being discovered that, on the contrary, these problems are increasingly affecting even the elderly. Along with other diseases that are considered characteristics of advanced age, such as cardiovascular, dysmetabolic, autoimmune, neurodegenerative, and oncological diseases, even FAs are increasingly frequent in the elderly. An FA is a pleiomorphic and multifactorial disease, characterized by an abnormal immune response and an impaired gut barrier function. The elderly exhibit distinct FA phenotypes, and diagnosis is difficult due to frequent co-morbidities and uncertainty in the interpretation of in vitro and in vivo tests. Several factors render the elderly susceptible to FAs, including the physiological changes of aging, a decline in gut barrier function, the skewing of adaptive immunity to a Th2 response, dysregulation of innate immune cells, and age-related changes of gut microbiota. Aging is accompanied by a progressive remodeling of immune system functions, leading to an increased pro-inflammatory status where type 1 cytokines are quantitatively dominant. However, serum Immunoglobulin E (IgE) levels and T helper type 2 (Th2 cytokine production have also been found to be increased in the elderly, suggesting that the type 2 cytokine pattern is not necessarily defective in older age. Dysfunctional dendritic cells in the gut, defects in secretory IgA, and decreased T regulatory function in the elderly also play important roles in FA development. We address herein the main immunologic aspects of aging according to the presence of FAs.
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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Disruption of the Gut Ecosystem by Antibiotics.
Yoon, MY, Yoon, SS
Yonsei medical journal. 2018;59(1):4-12
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The gut microbiome is a complex ecosystem of different micro-organisms, such as bacteria, viruses and fungi, living in the human intestines. It’s involved in numerous functions, such as extracting energy and nutrition from food, protecting against disease-causing microorganisms, and supporting the immune system of the host, and therefore affecting human health and disease. This paper is a review of studies on the effects of antibiotics on the gut microbiota. It outlines how different types of antibiotics can alter the intestinal environment and the composition of the microbes, resulting in various physiological changes that can trigger disease. Relevant mechanisms, such as inflammatory response and the use of intestinal nutrients by infectious bacteria are discussed. Finally, it discusses faecal microbiota transplantation (FMT) and probiotics as treatment approaches, aimed at restoring a disturbed intestinal environment.
Abstract
The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.
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Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.
Pagliari, D, Saviano, A, Newton, EE, Serricchio, ML, Dal Lago, AA, Gasbarrini, A, Cianci, R
Mediators of inflammation. 2018;2018:7946431
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Gut microbiota homeostasis plays a central role in modulating the mucosal immune system. Increasing research has shown a correlation between an imbalanced gut microbiota, called dysbiosis, and various pancreatic disorders. The aim of this review was to analyse current data linking the gut microbiome and several pancreatic disorders. The current evidence demonstrates gut dysbiosis is correlated with the duration and prognosis of pancreatic disorders. While this may lead to early detection of several pancreatic disorders, it remains unclear whether dysbiosis is a cause or effect of pancreatic disorders. Based on these results, the authors conclude future studies are required to better understand the crosstalk between gut microbiota and the immune system to improve diagnostic and treatment strategies for pancreatic disorders.
Abstract
Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.
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Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation.
Shen, ZH, Zhu, CX, Quan, YS, Yang, ZY, Wu, S, Luo, WW, Tan, B, Wang, XY
World journal of gastroenterology. 2018;24(1):5-14
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Ulcerative colitis (UC) is an inflammatory bowel disease that affects the large intestine. This review study looks at the evidence for intestinal bacteria (the gut microbiome) in triggering the disease and in treatment. It is not clear what causes UC, however it is believed to be an imbalance in the gut bacterial profile (a larger and/or smaller number of certain bacteria in comparison to normal) and the intestinal immune system, which leads to heightened inflammation. Therefore, intestinal dysbiosis (when the gut bacteria get out of balance) is thought to be part of the disease triggering mechanism. A meta-analysis of probiotic therapy in the treatment of active UC concluded that probiotics significantly increased the rate of disease remission, with the probiotic VSL#3 showing the most significant improvement. However, results of probiotics for UC treatment have not been consistent and more, larger randomised controlled trials are needed to clarify their role. Faecal microbiota transplantation also shows promise as a treatment in UC, however only limited evidence exists and efficacy is inconsistent.
Abstract
Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. However, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in the pathogenesis and treatment of UC.
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Inflammaging and the Lung.
Kovacs, EJ, Boe, DM, Boule, LA, Curtis, BJ
Clinics in geriatric medicine. 2017;33(4):459-471
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Characteristic of ageing is the presence of inflammatory markers in the blood and lead to the term inflammageing being coined. Inflammatory markers may contribute to chronic disease such as diseases of the lung. This review of 122 papers aimed to address the role of inflammageing on the lungs. The paper discussed the changes that the lungs immune cells go through with ageing and the impairment that they experience, with inflammageing playing a role. Causes of inflammageing were discussed and gut permeability, the halting of cell division and the stimulation of larger molecules in the body to release inflammatory markers were all implicated. Gut permeability which is a newer area of research with regards to inflammageing, was extensively discussed and allows more bacteria and pathogens into the body causing an inflammatory reaction. It was concluded that reducing inflammageing is a target for treatments in the elderly, whether these directly target inflammation or the underlying cause, requires more research. This paper could be used by healthcare professionals as a basis to understand inflammageing and where it may be appropriate to target inflammation in the elderly.
Abstract
With the coming of the "silver tsunami," expanding the knowledge about how various intrinsic and extrinsic factors affect the immune system in the elderly is timely and of immediate clinical need. The global population is increasing in age. By the year 2030, more than 20% of the population of the United States will be older than 65 years of age. This article focuses on how advanced age alters the immune systems and how this, in turn, modulates the ability of the aging lung to deal with infectious challenges from the outside world and from within the host.
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Early-Life Intestine Microbiota and Lung Health in Children.
Ranucci, G, Buccigrossi, V, de Freitas, MB, Guarino, A, Giannattasio, A
Journal of immunology research. 2017;2017:8450496
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In this short article the authors review important factors which influence the composition of the gut microbiome in early infancy. They then look at evidence for a “gut-lung axis" in the progression of chronic lung disease in children. They report that gut microbial composition is associated with disease progression in cystic fibrosis (CF) and development of childhood asthma. The authors also reviewed the use of prebiotics, probiotics and synbiotics (a combination of pre- and probiotics) in lung disease in children. They found that whilst in animal studies Lactobacilli have immunoregulatory effects on the lung, results of human clinical trials were variable, possibly due to the specific bacterial strains used. They report that clinical data are missing for probiotic intervention in the development of asthma. For CF, three randomised controlled trials found a beneficial effect of probiotics, in particular Lactobacillus GG and Lactobacillus reuteri, in disease progression and activity.
Abstract
The gastrointestinal microbiota plays a critical role in nutritional, metabolic, and immune functions in infants and young children and has implications for future lung health status. Understanding the role of intestinal dysbiosis in chronic lung disease progression will provide opportunities to design early interventions to improve the course of the disease. Gut microbiota is established within the first 1 to 3 years of life and remains relatively stable throughout the life span. In this review, we report the recent development in research in gut-lung axis, with focus on the effects of targeting microbiota of infants and children at risk of or with progressive lung diseases. The basic concept is to exploit this approach in critical window to achieve the best results in the control of future health.