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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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The Role of Lung and Gut Microbiota in the Pathology of Asthma.
Barcik, W, Boutin, RCT, Sokolowska, M, Finlay, BB
Immunity. 2020;52(2):241-255
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Over 300 million people suffer with asthma worldwide and it has emerged that microbiome analysis of the lung and gut bacteria, fungi, viruses, and archaea may help with disease management. This microbiome plays an important role in immune response. Disturbances to these microbes, known as dysbiosis, may influence onset of disease and the body’s ability to respond naturally, and/or to pharmaceutical treatments. Asthma is not a singular disease and there are great variations in symptom severity and underlying immune mechanisms. Patients are typically classified as type 2 or non-type 2. Type 2 patients tend to be allergic to common air-born allergens which can trigger an attack. Treatment usually consists of glucocorticosteroids or novel biologicals. Non type-2 asthma is associated with obesity-related asthma and typically responds poorly to steroid treatment. For a long time, researchers believed the human lungs to be sterile, so they were initially not included in the 2007 Human Microbiome Project. It has since been shown that, like the gut, the lungs and respiratory tract also host various microbes, and this healthy-airway microbiota influence innate and adaptive immune processes. The Gut-Lung axis also confers additional microbial benefits from the intestines. In asthma patients, there is often an over-dominance of pathogenic bacteria. Fungal dysbiosis is associated with high-risk asthma phenotypes in childhood. Viral infections have been shown as a primary cause of asthmatic episodes. Future diagnosis and treatment of patients with asthma should be assisted by analysis of the composition and metabolic activity of an individual’s microbiome.
Abstract
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
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Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections.
Calder, PC, Carr, AC, Gombart, AF, Eggersdorfer, M
Nutrients. 2020;12(4)
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Acute respiratory tract infections are a major cause of morbidity and mortality across the globe with seasonal influenza epidemics and outbreaks of viruses, such as Covid-19. The authors support public hygiene practices and the development of vaccinations however call for further strategies in order to reduce the impact that these infections have on societies. The role nutrition plays in supporting the immune system is well established. This review article and opinion piece presents the evidence for Vitamins A, B6, B12, C, D, E and folate; trace elements including zinc, selenium, magnesium and copper; and omega-3 fatty acids in supporting the immune system. The authors call for the consumption of a well-balanced diet, with additional supplementation of key immune supportive nutrients. Well referenced and with a helpful table of the rationale and recommended nutrient intake levels, Nutrition Practitioners will find this article useful when working to support client immune health.
Abstract
Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.
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Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus.
McCarty, MF, DiNicolantonio, JJ
Progress in cardiovascular diseases. 2020;63(3):383-385
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This highly technical review paper summarises some known actions and mechanisms by which certain nutraceuticals can boost the type 1 interferon response, a specific immune response to viruses, including influenza and coronavirus. These include: Ferulate (ferulic acid) has been shown to stimulate type 1 interferon production, and enhanced survival in influenza A-infected mice. Sulforaphane (phytochemical found in cruciferous vegetables like broccoli) and lipoic acid have similar actions. Spirulina extract has been found to decrease mortality in influenza-infected mice. Clinical and preclinical evidence for the potential benefits of N-acetylcysteine (NAC), a precursor for the important antioxidant glutathione, and selenium are also discussed. A glucosamine-enriched diet increased survival of mice infected with influenza virus. The authors present a table with suggested dosages for the above nutrients, as well as yeast beta-glucans, zinc and elderberry extracts, for viral control, whilst calling for more research into these compounds.
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The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.
Ilie, PC, Stefanescu, S, Smith, L
Aging clinical and experimental research. 2020;32(7):1195-1198
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The World Health Organisation declared COVID-19 caused by the virus SARS-CoV-2 a global pandemic. ACE-2 is the host cell receptor responsible for mediating infection by SARS-CoV-2. The main aim of this study was to assess the association between the mean levels of vitamin D in various countries and the mortality caused by COVID-19. A secondary aim was to identify any association/s between the mean vitamin D levels in various countries and the number of cases of COVID-19. This study is a cross-sectional analysis of based on studies carried out on European countries. Results indicate a potential crude association between the mean vitamin D levels in various European countries with COVID-19 cases and COVID-19 mortality. Authors conclude that further studies about vitamin D levels in COVID-19 patients with different degrees of disease severity should be performed.
Abstract
WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.
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The impact of nutrition on COVID-19 susceptibility and long-term consequences.
Butler, MJ, Barrientos, RM
Brain, behavior, and immunity. 2020;87:53-54
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The impacts of Covid-19 are being felt across the world, affecting health, healthcare and economies. Statistics from across the world are showing that the elderly, those with underlying medical conditions and under-represented minority groups are particularly vulnerable to severe complications and have a higher risk of dying of Covid-19. This opinion piece presents arguments for the importance of focusing on diet to support health resilience in general and the immune system in particular, to minimise the impact of this and future viruses. Research is presented on excessive intake of saturated fat leading to chronic activation of the innate immune system (first line, rapid defence against infection), resulting in inflammation, and associated heightened susceptibility to complications of viral infection. The standard western diet (high saturated fat, refined carbohydrates and sugars, low levels of fibre, unsaturated fat and antioxidants) has also been shown to affect the adaptive immune system (second line, delayed defence against infection), depressing its action against infection. The piece also discusses possible long-term, future impacts of those recovered from Covid-19 infection, particularly in relation to neurodegenerative diseases such as Alzheimer’s. The authors call for fresh, healthy wholefoods to be readily available and affordable to everyone in society.
Abstract
While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type 2 diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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The Malnutritional Status of the Host as a Virulence Factor for New Coronavirus SARS-CoV-2.
Briguglio, M, Pregliasco, FE, Lombardi, G, Perazzo, P, Banfi, G
Frontiers in medicine. 2020;7:146
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This opinion article explores the role of an individual’s nutrition status when subjected to infection by viruses, in particular Covid-19. Distinction is made between the susceptibility to infection in the first instance and the ability to persist in fighting infection once it is established. For Covid-19, it is argued that a healthier nutritional status, in particular Vitamins A, B, C, D and E, iron selenium and zinc, will lower susceptibility to infection, lower the severity of the virus and therefore reduce the length of time an individual has to find reserves to fight the virus. More severe cases of Covid-19 infection also often include gastro-intestinal symptoms which further exacerbate nutritional status with lowered appetite. The authors conclude that malnourished individuals may be more susceptible to Covid-19 infection and that nutritional support is vital in severe cases. The article includes a useful diagram of both hyponutrition and hypernutrition and possible impacts of Covid-19.
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Is copper beneficial for COVID-19 patients?
Raha, S, Mallick, R, Basak, S, Duttaroy, AK
Medical hypotheses. 2020;142:109814
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Copper (Cu) is an essential micronutrient that plays an important role in both the innate and adaptive immune response. It has been shown that Cu-deficient humans show increased susceptibility to viral infections. While there is no current vaccine or drug available for the novel coronavirus SARS-CoV-2 (COVID-19), it is critical to identify ways to slow the spread until treatments are found. The aim of this study was to review available data and explore whether increased Cu-levels can boost the immunity in people at risk of COVID-19. While there is a definitive need for clinical trials, the available research does show an association between Cu-deficiency and a weakened immune system. Also, current models for optimal Cu intake indicate that a large portion of the United States population may have Cu-deficiency. Based on this available data, the authors conclude that Cu supplementation may have a protective effect against COVID-19, especially in people at risk for Cu-deficiency.
Abstract
Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS-CoV-2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS-CoV-2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19.
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COVID-19 infection: the perspectives on immune responses.
Shi, Y, Wang, Y, Shao, C, Huang, J, Gan, J, Huang, X, Bucci, E, Piacentini, M, Ippolito, G, Melino, G
Cell death and differentiation. 2020;27(5):1451-1454
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The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inflammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.
