scholarly journals Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021

2021 ◽  
pp. 1-16
Author(s):  
Ashley M. Queener ◽  
Sergio E. Chiarella ◽  
Lyda Cuervo-Pardo ◽  
Mackenzie E. Coden ◽  
Hiam Abdala-Valencia ◽  
...  
Keyword(s):  
Allergic Disease ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Airway Disease ◽  
Epithelial Barrier ◽  
Metabolic Dysfunction ◽  
New Research

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.

scholarly journals Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander L. Pendleton ◽  
Stephanie R. Wesolowski ◽  
Timothy R. H. Regnault ◽  
Ronald M. Lynch ◽  
Sean W. Limesand
Keyword(s):  
Skeletal Muscle ◽  
Nutrient Availability ◽  
Energy Demand ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Substrate Utilization ◽  
Nutrient Concentrations ◽  
Metabolic Dysfunction ◽  
Intrauterine Growth ◽  
Fetal Survival

Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver. For example, cellular energy production and metabolic rate are decreased in the skeletal muscle and liver of IUGR fetuses. These metabolic adaptations demonstrate that fundamental processes in mitochondria, such as substrate utilization and oxidative phosphorylation, are tempered in response to low oxygen and nutrient availability. As a central metabolic organelle, mitochondria coordinate cellular metabolism by coupling oxygen consumption to substrate utilization in concert with tissue energy demand and accretion. In IUGR fetuses, reducing mitochondrial metabolic capacity in response to nutrient restriction is advantageous to ensure fetal survival. If permanent, however, these adaptations may predispose IUGR fetuses toward metabolic diseases throughout life. Furthermore, these mitochondrial defects may underscore developmental programming that results in the sequela of metabolic pathologies. In this review, we examine how reduced nutrient availability in IUGR fetuses impacts skeletal muscle and liver substrate catabolism, and discuss how enzymatic processes governing mitochondrial function, such as the tricarboxylic acid cycle and electron transport chain, are regulated. Understanding how deficiencies in oxygen and substrate metabolism in response to placental restriction regulate skeletal muscle and liver metabolism is essential given the importance of these tissues in the development of later lifer metabolic dysfunction.

scholarly journals The association of different enteroviruses with atopy and allergic diseases in early childhood

2021 ◽  
Author(s):  
Tiina Palmu ◽  
Jussi Lehtonen ◽  
Laura Korhonen ◽  
Suvi Virtanen ◽  
Onni Niemelä ◽  
...  
Keyword(s):  
Early Childhood ◽  
Allergic Disease ◽  
Allergic Sensitization ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Specific Ige ◽  
Case Control ◽  
Inverse Association ◽  
Factors Influencing ◽  
Nested Case Control

Background: Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association of EVs with allergic sensitization and disease in early childhood. Methods: The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and asked with ISAAC questionary. We screened for the presence of serotype specific antibodies against 41 EVs at 1 to 5 years of age and assessed their association with allergic sensitization and disease. Results: The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95 % CI 0.36-0.99), P = 0.048. Conclusion: This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.

The prevalence of allergic diseases -The prevalence of atopic disease is decreasing・ from the surveillance in Himeji-

2014 ◽  
Vol 28 (1) ◽  
pp. 50-57
Author(s):  
Fumitake Kurosaka ◽  
Kazuta Shimizu ◽  
Katsumi Oka ◽  
Shigeta Shimizu ◽  
Hironobu Takahashi ◽  
...  
Keyword(s):  
Allergic Diseases ◽  
Atopic Disease

Non-pharmacological Strategies Against Systemic Inflammation: Molecular Basis and Clinical Evidence

2020 ◽  
Vol 26 (22) ◽  
pp. 2620-2629 ◽  
Author(s):  
Rita Del Pinto ◽  
Davide Pietropaoli ◽  
Annalisa Monaco ◽  
Giovambattista Desideri ◽  
Claudio Ferri ◽  
...  
Keyword(s):  
Human Genome ◽  
Systemic Inflammation ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Lifestyle Changes ◽  
Common Denominator ◽  
Active Lifestyle ◽  
Systemic Impact ◽  
Public Health Strategies

Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders, and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management of these conditions. We performed an updated narrative review on the mechanisms behind the systemic impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate the resident microbial community. To date, evidence from high-quality human studies is sparse to allow the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the mechanisms behind future personalized medicine.

scholarly journals Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—A Condition Associated with Heightened Sympathetic Activation

2021 ◽  
Vol 22 (8) ◽  
pp. 4241
Author(s):  
Revathy Carnagarin ◽  
Kearney Tan ◽  
Leon Adams ◽  
Vance B. Matthews ◽  
Marcio G. Kiuchi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Treatment Strategies ◽  
Adverse Outcomes ◽  
Metabolic Dysfunction ◽  
Sympathetic Activation ◽  
Beneficial Effects ◽  
Adverse Health Outcomes

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

scholarly journals Impact of diet on the immunological microenvironment of the pregnant uterus and its relationship to allergic disease in the offspring: a review of the recent literature

2006 ◽  
Vol 124 (5) ◽  
pp. 298-303 ◽  
Author(s):  
Daniella Campelo Batalha Cox Moore ◽  
Pedro Xavier Elsas ◽  
Elisabeth Santos Maximiano ◽  
Maria Ignez Capella Gaspar Elsas
Keyword(s):  
Allergic Disease ◽  
Allergic Diseases ◽  
Perinatal Period ◽  
Time Interval ◽  
Industrialized Countries ◽  
Pregnant Uterus ◽  
Medical Progress ◽  
Immunological Profile ◽  
Dietary Content ◽  
The Relationship

Medical progress has reduced the mortality from infectious diseases in most countries, but allergic diseases have become more prevalent worldwide over the same period, especially in industrialized countries. This has prompted speculation that modern lifestyles have altered the relationship between heredity and environment so as to promote development of an atopic phenotype when exposure to infection decreases. A healthy uterine microenvironment is known to favor Th2 lymphocyte development. However, some evidence suggests that persistence of the Th2 pattern of immunity directs the developing organism's immune response towards a long-lasting atopic phenotype. Even though the outcome also depends on other factors (such as infection, functional state of the intestinal microflora, and exposure to environmental allergens at times critical to development), it seems that the immune system during the perinatal period is responsive to interventions that are no longer effective in adulthood. We have reviewed the literature accessible through Medline to identify recent advances in the prevention of allergic disease through interventions in the fetal-maternal relationship. Diet seems to have a significant impact on the immunological profile of the pregnant uterus, as well as on the postnatal development of allergic disease in the offspring, as suggested by the effects of probiotic bacteria and by manipulations of the dietary content of polyunsaturated fatty acids and antioxidants. This highlights the need for further studies, in order to define the best intervention methods, the most appropriate time interval and the individuals who will most likely benefit from them.

scholarly journals The Role of Hydrolyzed Formula in Allergy Prevention

2017 ◽  
Vol 70 (Suppl. 2) ◽  
pp. 38-45 ◽  
Author(s):  
Michael D. Cabana
Keyword(s):  
Allergic Rhinitis ◽  
Food Allergy ◽  
Infant Formula ◽  
Allergic Disease ◽  
Clinical Studies ◽  
Atopic Disease ◽  
Allergy Prevention ◽  
Preventive Effect ◽  
History Of ◽  
Hydrolyzed Formula

Asthma, eczema, food allergy, and allergic rhinitis are some of the most common pediatric, chronic conditions in the world. Breastfeeding is the optimal way to feed all infants. For those infants who are exposed to infant formula, some studies suggest that certain partially hydrolyzed or extensively hydrolyzed formulas may decrease the risk of allergic disease compared to nonhydrolyzed formulas for children with a family history of atopic disease. Overall, there is some evidence to suggest that partially hydrolyzed whey formulas and extensively hydrolyzed casein formulas may decrease the risk of developing eczema for infants at high risk of allergic disease. The evidence for a preventive effect of hydrolyzed formulas on allergic rhinitis, food allergy, and asthma is inconsistent and insufficient. Finally, the qualitative changes to the peptides by the method of hydrolysis, not just the degree of protein hydrolysis, may have a large influence on the preventive effect of a particular infant formula for the potential risk of allergic disease. As a result, it may be difficult to generalize findings from clinical studies using a specific infant formula to other infant formulas from different manufacturers using different methods of hydrolysis. Further clinical studies are needed to help clinicians identify which infants may benefit from early intervention, as well as which specific hydrolyzed formulas are best suited to decrease the risk of future allergic disease.

scholarly journals Mosquito hypersensitivity may be associated with atopic background in children

2021 ◽  
Vol 49 (6) ◽  
pp. 67-72
Author(s):  
Süleyman Tolga Yavuz ◽  
Onur Akin ◽  
Ozan Koc ◽  
Ali Gungor ◽  
Ahmet Bolat ◽  
...  
Keyword(s):  
Grass Pollen ◽  
Matched Control ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Duration Of Symptoms ◽  
Prick Test ◽  
Pediatric Allergy ◽  
Systemic Reactions ◽  
Dust Mite ◽  
Children With Asthma

Background: Many children encounter unusual or “exaggerated” reactions such as large local, atypical or systemic reactions after mosquito bites.Objective: The aim of this study was to document the clinical features of children with mos-quito allergy and investigate the possible associations between demographic features and type of reactions in this population.Methods: Children with large local or unusual reactions after mosquito bites who attended to our outpatient pediatric allergy department were enrolled in the study along with control subjects.Results: A total of 180 children (94 with mosquito allergy and 86 age and sex-matched control subjects) with a median age of 6.8 years (IQR 5.5–9.3) were enrolled. Atopy (35.1% vs. 11.6%, p < 0.001) and grass pollen sensitization (28.7% vs. 8.1%, p < 0.001) were significantly more frequent in children with mosquito allergy. Skin prick test with mosquito allergen was positive in only 6 children (6,4%). Grass pollen sensitization was most common in children (28.7%) followed by sensitization to house dust mite (9.6%). 30 children (31.9%) had an accompanying atopic disease such as allergic rhinitis, asthma or atopic dermatitis. Bullae were significantly more frequent in children with asthma (41.7% vs.15.9, p = 0.034). The median duration of symptoms after onset were significantly longer in patients with ecchymosis, with immediate wheals and in children whose symptoms start in 20 min to 4 hours after mosquito bites.Conclusion: There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background.

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

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