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1.
A cross talk between microbial metabolites and host immunity: Its relevance for allergic diseases.
Losol, P, Wolska, M, Wypych, TP, Yao, L, O'Mahony, L, Sokolowska, M
Clinical and translational allergy. 2024;(2):e12339
Abstract
BACKGROUND Allergic diseases, including respiratory and food allergies, as well as allergic skin conditions have surged in prevalence in recent decades. In allergic diseases, the gut microbiome is dysbiotic, with reduced diversity of beneficial bacteria and increased abundance of potential pathogens. Research findings suggest that the microbiome, which is highly influenced by environmental and dietary factors, plays a central role in the development, progression, and severity of allergic diseases. The microbiome generates metabolites, which can regulate many of the host's cellular metabolic processes and host immune responses. AIMS AND METHODS Our goal is to provide a narrative and comprehensive literature review of the mechanisms through which microbial metabolites regulate host immune function and immune metabolism both in homeostasis and in the context of allergic diseases. RESULTS AND DISCUSSION We describe key microbial metabolites such as short-chain fatty acids, amino acids, bile acids and polyamines, elucidating their mechanisms of action, cellular targets and their roles in regulating metabolism within innate and adaptive immune cells. Furthermore, we characterize the role of bacterial metabolites in the pathogenesis of allergic diseases including allergic asthma, atopic dermatitis and food allergy. CONCLUSION Future research efforts should focus on investigating the physiological functions of microbiota-derived metabolites to help develop new diagnostic and therapeutic interventions for allergic diseases.
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2.
Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients.
Roth-Walter, F, Berni Canani, R, O'Mahony, L, Peroni, D, Sokolowska, M, Vassilopoulou, E, Venter, C
Allergy. 2024;(2):353-383
Abstract
Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non-communicable diseases-where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.
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3.
Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.
Untersmayr, E, Venter, C, Smith, P, Rohrhofer, J, Ndwandwe, C, Schwarze, J, Shannon, E, Sokolowska, M, Sadlier, C, O'Mahony, L
International archives of allergy and immunology. 2024;:1-14
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. SUMMARY In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. KEY MESSAGES Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.
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4.
Interactions between microbiome and underlying mechanisms in asthma.
Losol, P, Sokolowska, M, Chang, YS
Respiratory medicine. 2023;:107118
Abstract
Microbiome primes host innate immunity in utero and play fundamental roles in the development, training, and function of the immune system throughout the life. Interplay between the microbiome and immune system maintains mucosal homeostasis, while alterations of microbial community dysregulate immune responses, leading to distinct phenotypic features of immune-mediated diseases including asthma. Microbial imbalance within the mucosal environments, including upper and lower airways, skin, and gut, has consistently been observed in asthma patients and linked to increased asthma exacerbations and severity. Microbiome research has increased to uncover hidden microbial members, function, and immunoregulatory effects of bacterial metabolites within the mucosa. This review provides an overview of environmental and genetic factors that modulate the composition and function of the microbiome, and the impacts of microbiome metabolites and skin microbiota on immune regulation in asthma.
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5.
Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases.
Losol, P, Sokolowska, M, Hwang, YK, Ogulur, I, Mitamura, Y, Yazici, D, Pat, Y, Radzikowska, U, Ardicli, S, Yoon, JE, et al
Allergy, asthma & immunology research. 2023;(6):705-724
Abstract
Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence.
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6.
Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.
Vlieg-Boerstra, B, de Jong, N, Meyer, R, Agostoni, C, De Cosmi, V, Grimshaw, K, Milani, GP, Muraro, A, Oude Elberink, H, Pali-Schöll, I, et al
Allergy. 2022;(5):1373-1388
Abstract
It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2 = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.
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7.
Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma.
Wirz, OF, Jansen, K, Satitsuksanoa, P, van de Veen, W, Tan, G, Sokolowska, M, Mirer, D, Stanić, B, Message, SD, Kebadze, T, et al
Allergy. 2022;(1):130-142
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Abstract
BACKGROUND Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. METHODS We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA-sequencing. Rhinovirus-derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B-cell differentiation in response rhinovirus stimulation. Protein expression of pro-inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. RESULTS B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN-alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co-stimulation with rhinovirus and IFN-alpha upregulated pro-inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. CONCLUSION These findings add to the understanding of systemic effects of rhinovirus infections on B-cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.
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Role of dietary fiber in promoting immune health-An EAACI position paper.
Venter, C, Meyer, RW, Greenhawt, M, Pali-Schöll, I, Nwaru, B, Roduit, C, Untersmayr, E, Adel-Patient, K, Agache, I, Agostoni, C, et al
Allergy. 2022;(11):3185-3198
Abstract
Microbial metabolism of specific dietary components, such as fiber, contributes to the sophisticated inter-kingdom dialogue in the gut that maintains a stable environment with important beneficial physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber-derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision-making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, the importance of appropriate timing of intervention to target any potential window of opportunity, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions, and outcomes were too heterogeneous for meta-analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health.
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Risk factors for severe and critically ill COVID-19 patients: A review.
Gao, YD, Ding, M, Dong, X, Zhang, JJ, Kursat Azkur, A, Azkur, D, Gan, H, Sun, YL, Fu, W, Li, W, et al
Allergy. 2021;(2):428-455
Abstract
The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.
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Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases.
Tramper-Stranders, G, Ambrożej, D, Arcolaci, A, Atanaskovic-Markovic, M, Boccabella, C, Bonini, M, Karavelia, A, Mingomataj, E, O' Mahony, L, Sokolowska, M, et al
Allergy. 2021;(11):3276-3291
Abstract
Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.