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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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Presence of positive skin prick tests to inhalant allergens and markers of T2 inflammation in subjects with chronic spontaneous urticaria (CSU): a systematic literature review.
Wong, MM, Keith, PK
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2020;16:72
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Urticaria is an immune driven skin reaction, which manifests as hives and swelling and results in significantly decreased quality of life in those who suffer from it. The causes are currently unknown, however airborne substances such as house dust mites and plant pollen may play a role in its development. This systematic review and meta-analysis of 18 studies aimed to determine the role of airborne allergens in the development of chronic spontaneous urticaria (CSU). The results showed that individuals with CSU were more likely to have a sensitivity to airborne allergens and that house dust mites were a leading cause of sensitivity. It was concluded that airborne associated sensitivity is of importance to the development of CSU. This study could be used by healthcare professionals to understand that airborne allergens may be a cause of CSU and that house dust mites may be involved in its development. It is important to determine the cause and eliminate it, to increase the chances of successful treatment.
Abstract
BACKGROUND Current guidelines do not recommend performing aeroallergen skin prick testing (SPT) in chronic spontaneous urticaria (CSU). OBJECTIVE The objective of this review was to investigate the presence of aeroallergen sensitization and markers of T2 inflammation in subjects with CSU. METHODS Systematic literature reviews to identify all studies that evaluated the presence of T2 markers of allergic inflammation in CSU subjects were performed. RESULTS In 16 studies that assessed the prevalence of positive SPT to multiple aeroallergens in CSU, 38.5% of CSU subjects had positive SPT. In three controlled studies, 34.2% of CSU subjects had positive SPT to multiple aeroallergens, compared to 13.6% of controls (p = 0.047). In 18 studies that assessed the prevalence of house dust mite (HDM) positive SPT in CSU, 27.5% of CSU subjects had positive SPT. In three controlled studies, 27.5% of CSU subjects had positive SPT to HDM, compared to 2.1% of controls (p = 0.047). Overall, CSU subjects were 3.1 times more likely to be aeroallergen-sensitized (95% CI 1.7-5.8, p = 0.0002) and 6.1 times more likely to be HDM-sensitized (95% CI 3.7-9.9, p < 0.00001) than controls. Mean total serum IgE (tIgE) levels were 238 kU/L and median tIgE levels were 164 kU/L, which was greater than the upper 90th percentile of normal (< 137 kU/L). Compared to healthy controls, CSU subjects were 6.5 times more likely to have IgG autoantibody against FcεR1α (p = 0.001), 2.4 times more likely to have IgG anti-IgE antibody (p = 0.03) and 5 times more likely to have anti-thyroid peroxidase (anti-TPO) antibody (p = 0.02). When corticosteroids were withheld for ≥ 28 days, mean blood eosinophil percentage was elevated at 5.9% (normal < 4%), but other studies reporting absolute count found the mean was in the normal range, 239 × 10 6 / L (normal < 400 × 10 6 / L). CONCLUSION Increased aeroallergen sensitization, tIgE, autoantibodies and blood eosinophil percentage in the CSU subjects indicates the possible importance of T2 inflammation in the pathogenesis of CSU. Further studies may be warranted to determine if specific allergen avoidance, desensitization or improvement in the mucosal allergic inflammation present in asthma and/or rhinitis has any benefit in the management of CSU.
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The role of diet and probiotics in prevention and treatment of bacterial vaginosis and vulvovaginal candidiasis in adolescent girls and non-pregnant women.
Mizgier, M, Jarzabek-Bielecka, G, Mruczyk, K, Kedzia, W
Ginekologia polska. 2020;91(7):412-416
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In adolescent girls and non-pregnant women, vaginitis, including fungal infections, is a common problem. Vaginitis clinically manifests as abnormal vaginal discharge, irritation, itching, burning and discomfort, and is especially prevalent with a decrease in immunity. The normal bacterial flora of the vagina and cervix protect against the development of pathogenic strains, while abnormal flora tend to be the most common starting point for the development of infections. The aim of this study was to determine the role of proper diet and probiotics and prebiotics use in relation to therapy and prophylaxis of vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in non-pregnant women and girls. This review shows that: - An unbalanced diet can be a risk factor for BV. Women tend to be more exposed to BV if they have poor micronutrient status, including vitamins A, E, D, C and beta carotene — indicating a lower fruit and vegetable intake. - Many studies proved that regulated use of probiotics, administered both orally and vaginally, are effective in the prevention and treatment of vaginal infections such as BV and VVC. - To create a positive environment for probiotics, it is important to provide prebiotics that support the development of probiotic strains. Authors conclude that gynaecologists, obstetricians, general practitioners and dieticians should share their findings, and raise awareness among the general population as to the importance of optimal nutrition. Probiotics and prebiotics could be considered to prevent infections of the genital tract, reduce associated disease, and maintain reproductive health.
Abstract
The article raises important issues regarding the use of diet and probiotics in prevention and treatment of vaginitis. Vaginitis is defined as any condition with symptoms of abnormal vaginal discharge. The most common causes of vaginitis are vulvovaginal candidiasis (VVC), trichomoniasis and bacterial vaginosis (BV). Vaginitis has been linked to itching, burning, pain, discharge, irritation and also adverse reproductive and obstetric health outcomes. Moreover, microorganisms that build vaginal flora in the state of bacterial vaginosis are a source of cervicitis and endometritis (often in subclinical forms) and pelvic inflammatory disease (PID) The proper diet and probiotics consumption may influence the composition of the gut microbiota, improve gut integrity, and have an impact on maintaining and recovering the normal vaginal microbiota. Future studies and reviews investigating the role of diet and probiotics in changes to gut and vaginal microbiome need to focus on deciphering the mechanismus of host bacteria interaction in vulvovaginal health.
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Raw Cow's Milk and Its Protective Effect on Allergies and Asthma.
Sozańska, B
Nutrients. 2019;11(2)
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In the last decades, a significant increase in the prevalence of allergic diseases and asthma has been observed. Living on a farm can reduce the risk of allergen sensitisation and allergic diseases in children. Most proposed explanations have been based on variations in the “hygiene hypothesis” and a possible effects on immune balance of a farm environment. Here, the author reviews epidemiological and experimental evidence for the documented protective effects of unpasteurised milk on allergies and asthma. Epidemiological studies from a number of countries show that children who consume raw milk early in life are less likely to develop allergies, independent of other factors. In one study that looked into possible components for this effect found that certain milk proteins (α-lactalbumin, β-lactoglobulin, and bovine serum albumin whey protein) reduced the risk of developing asthma . Total fat and protein content, amount of bacteria in the milk, and lactose levels were not associated with allergies or asthma. Another study found that higher levels of total fat and of omega-3 polyunsaturated fatty acids in raw milk had protective effects. The author discusses differences between raw and treated milk. Homogenisation changes the physical structure of fats and proteins, resulting in casein proteins being more easily adsorbed. The aim of heating milk, either through pasteurisation or UHT sterilisation, is to reduce bacterial numbers and growth, but it also affects heat-sensitive milk components, including whey proteins, immunoglobulins and lactoferrin, which have been shown to modulate the immune system. The author concludes that components of raw milk can influence immune function, and acknowledges the controversy with regards to raw milk carrying a risk of bacterial pathogens and that a proof based on controlled studies in infants is not possible due to ethical reasons.
Abstract
Living on a farm and having contact with rural exposures have been proposed as one of the most promising ways to be protected against allergy and asthma development. There is a significant body of epidemiological evidence that consumption of raw milk in childhood and adulthood in farm but also nonfarm populations can be one of the most effective protective factors. The observation is even more intriguing when considering the fact that milk is one of the most common food allergens in childhood. The exact mechanisms underlying this association are still not well understood, but the role of raw milk ingredients such as proteins, fat and fatty acids, and bacterial components has been recently studied and its influence on the immune function has been documented. In this review, we present the current understanding of the protective effect of raw milk on allergies and asthma.
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Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions.
Duggal, NA
Biogerontology. 2018;19(6):481-496
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Advancing age is accompanied by a compromised ability of older adults to combat bacterial and viral infections, increased risk of autoimmunity, poor vaccination responses and the re-emergence of latent infections. This review discusses current understanding of immunesenescence [the gradual deterioration of our immune system as we get older] and also focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals. Findings show that: - changes in nutrition and lifestyle can be an effective approach towards improving immune outcome in older adults but may be hard to achieve at a population level. - improving immune responses, such as the developments of vaccines, may be used as an early biomarker for anti-ageing effects. Authors conclude that immunomodulation represents a promising therapeutic approach to improve the health of older adults.
Abstract
It is widely accepted that ageing is accompanied by remodelling of the immune system, including reduced numbers of naïve T cells, increased senescent or exhausted T cells, compromise to monocyte, neutrophil and natural killer cell function and an increase in systemic inflammation. In combination these changes result in increased risk of infection, reduced immune memory, reduced immune tolerance and immune surveillance, with significant impacts upon health in old age. More recently it has become clear that the rate of decline in the immune system is malleable and can be influenced by environmental factors such as physical activity as well as pharmacological interventions. This review discusses briefly our current understanding of immunesenescence and then focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals.
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The gut microbiome and irritable bowel syndrome.
Menees, S, Chey, W
F1000Research. 2018;7
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This study is a review of role of gut microbiome plays in the pathophysiology of Irritable bowel syndrome (IBS) sufferers. The author’s main objective was to identify the biomarkers that may lead into diagnosing and choosing best available therapy available from various interventions available for IBS that targets the gut microbiome, such as prebiotics, probiotics, non-absorbable antibiotics, diet and faecal microbial transplant (FMT). The authors concluded that to enable the right treatment for IBS sufferers it would be better to understand what constitutes a healthy gut rather than deciphering what is abnormal.
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders encountered in clinical practice. It is a heterogeneous disorder with a multifactorial pathogenesis. Recent studies have demonstrated that an imbalance in gut bacterial communities, or "dysbiosis", may be a contributor to the pathophysiology of IBS. There is evidence to suggest that gut dysbiosis may lead to activation of the gut immune system with downstream effects on a variety of other factors of potential relevance to the pathophysiology of IBS. This review will highlight the data addressing the emerging role of the gut microbiome in the pathogenesis of IBS and review the evidence for current and future microbiome based treatments.
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The microbiome and autoimmunity: a paradigm from the gut-liver axis.
Li, B, Selmi, C, Tang, R, Gershwin, ME, Ma, X
Cellular & molecular immunology. 2018;15(6):595-609
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The incidence of autoimmune and inflammatory diseases has been increasing worldwide. Changes in environmental factors, such as modern lifestyle, diet, antibiotics and hygiene are thought to play a critical role in the development of various autoimmune diseases. It is the mucosal microbial flora that is shaped by our environment and communicates with the innate and adaptive immune systems, and when disrupted, can lead to the loss of immune tolerance and dysregulated immune cells. This review paper provides an overview of the interactions between the intestinal microbiome and the immune system. It explains how these interactions affect host autoimmunity locally and systemically and sheds light on the molecular mechanisms, utilised by microbes that may contribute to systemic autoimmunity in genetically susceptible individuals. The links between the gut microbiome and various autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, as well as the gut-liver axis, involving intestinal microbiome and autoimmune liver diseases, are discussed in more detail.
Abstract
Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut-liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.
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Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
Newberry, F, Hsieh, SY, Wileman, T, Carding, SR
Clinical science (London, England : 1979). 2018;132(5):523-542
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Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease. Several studies have shown alterations in the gut microbiome (dysbiosis) in patients with ME/CFS. However, in focusing on the bacterial components of the microbiome, the viral component of the microbiome (known as the virome) has been neglected. Viruses can change the microbiome which can influence the health. This area is therefore important for research into ME/CFS. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the challenges associated with microbiome studies are discussed. A literature search was done and 11 papers were found that had examined the microbiome ME/CFS patients, dating from 1998 to 2017. It was not possible to compare the studies statistically but from looking at each one individually there is sufficient evidence to support the claim of an altered intestinal microbiome in ME/CFS patients. ME/CFS is multifactorial and potential dysbiosis should be considered to be only part of the picture. Future studies are needed to adopt standardized techniques and analyses. As research increases, it is becoming clear that the virome can directly and indirectly affect host health, and may play a role in the pathogenesis of ME/CFS.
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.