Prevention Of Atopic Dermatitis Research Articles

How to prevent Atopic Dermatitis (Eczema) in 2024: theory and evidence

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease characterized by dry, itchy, and inflamed skin. We review emerging concepts and clinical evidence addressing the pathogenesis and prevention of atopic dermatitis. We review several interventions ranging from skin barrier enhancement strategies; probiotics, prebiotics, and synbiotics, and conversely, antimicrobial exposure; vitamin D and omega fatty acid supplementation; breastfeeding and hydrolyzed formula; house dust mite avoidance and immunotherapy. We appraise the available evidence base within the context of the GRADE approach. We also contextualize our findings in relation to concepts relating atopic dermatitis and individual-patient allergic life trajectories versus a linear concept of the atopic march and provide insights into future knowledge gaps and clinical trial design considerations that must be addressed in future research. Finally, we provide implementation considerations to detect population-level differences in AD risk. Major international efforts are required to provide definitive evidence regarding what works, and what does not, for preventing AD.

Filaggrin Mutation Status and Prevention of Atopic Dermatitis with Maternal Probiotic Supplementation.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n =   228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Neonatal Filaggrin Genetic Screening and Counseling to Prevent Atopic Dermatitis in High-Risk Infants.

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

The Beneficial Role of Lactobacillus paracasei subsp. paracasei NTU 101 in the Prevention of Atopic Dermatitis.

Atopic dermatitis (AD) is a recurrent allergic disease characterized by symptoms such as itching, redness, swelling, dryness, scaling skin, inflammation, and tissue damage. The underlying pathogenesis of AD remains unclear. Steroid drugs are commonly used in the clinical treatment of AD; however, their long-term use may lead to associated complications. Numerous studies have indicated that probiotics could modulate the immune system, enhance immune function, or suppress excessive immune responses. In this study, Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) was orally administered for a duration of 4 weeks, followed by the induction of AD using ovalbumin (OVA) in a mouse model. The skin condition of the stimulated site was observed during the induction period. Subsequently, the serum immunoglobulin E (IgE) content, splenocyte T cell typing, and skin histological interpretation were examined to evaluate the efficacy of NTU 101 in alleviating AD symptoms in allergen-exposed animals. The findings indicated that administering NTU 101 beforehand effectively alleviated skin symptoms in animals with AD. It reduced the infiltration of inflammatory cells in skin tissue sections, and compared to the OVA group, there was a significant reduction in the thickening of the epidermal cell layer (decreased from 89.0 ± 20.2 µM to 48.6 ± 16.0 µM) and dermis layer (decreased from 310.3 ± 69.0 µM to 209.7 ± 55.5 µM). Moreover, the proportion of regulatory T (Treg) cells and T helper 2 (Th2) cells in splenocytes significantly increased, while the proportions of T helper 1 (Th1) and T helper 17 (Th17) cells did not differ. It is speculated that the potential mechanism by which NTU 101 prevents AD involves increasing the expression of Forkhead box protein P3 (FOXP3) and promoting Treg cell maturation, thereby alleviating allergic reaction symptoms associated with AD.

Biotics and Children's and Adolescents' Health: A Narrative Review.

Recently, there has been an increasing interest in the association of gut microbiota with health conditions and the potentially beneficial role of several types of biotics in several population groups, including children and adolescents. Children and adolescents comprise a unique population group due their rapid growth rates, high nutritional requirements, the immaturity of their immune system in early life, and their susceptibility to infectious diseases. The aim of the present study is to investigate the role and limitations of the administration of biotics in specific conditions affecting children and adolescents. A narrative review of related articles published on PubMed up to October 2023 was conducted. The administration of biotics has been evaluated in several health conditions among children and adolescents, such as the treatment and prevention of infectious diarrhea, the prevention of diarrhea after the use of antibiotics, the prevention of necrotizing enterocolitis, the treatment of functional gastrointestinal diseases, such as infant colic, functional abdominal pain, and irritable bowel syndrome, the eradication of H. pylori, the treatment of ulcerative colitis and pouchitis, and the prevention of atopic dermatitis, and the findings indicate improved symptoms and various beneficial health outcomes. However, some limitations have been identified regarding probiotics' use. In conclusion, biotics may have a beneficial impact in several health conditions among children and adolescents. There is a need for additional randomized, controlled clinical studies on the effects of the administration of biotics in children and particularly in adolescents and young adults.

Role of skin management in the prevention of atopic dermatitis and food allergy.

Food allergy is postulated to originate from cutaneous sensitization through a disrupted skin barrier, particularly in atopic dermatitis (AD). Strategies for food allergy prevention currently centre around early allergic food introduction, but there is now increasing evidence for the role of early skin barrier restoration in the form of prophylactic emollient therapy and early aggressive, proactive treatment of established AD for food allergy prevention. Research gaps that remain to be addressed include the type of emollient or anti-inflammatory medication, which confers the greatest efficacy in preventive or proactive skin treatment, respectively, the duration of therapy, and the window of opportunity for these interventions.

Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFβ, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFβ and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

Should Emollients Be Recommended for the Prevention of Atopic Dermatitis?—New Evidence and Current State of Knowledge

Introduction: Atopic dermatitis (AD) is a chronic, pruritic skin disease with complex pathogenesis, which affects about 43 million children aged 1–4 years. One of the most known methods of alleviating symptoms of AD is emollient treatment, which varies depending on formulation and additional active ingredients. There is some evidence that emollients could be used in AD prevention in high-risk children. Materials and methods: A search of the literature from Cochrane Library, PubMed and Medline was conducted between August and September 2023 with the following keywords: “atopic dermatitis”, “emollients”, and “prevention”. Only randomised clinical trials published in the last 5 years were included into the meta-analysis. Results: Considering the inclusion criteria only 11 randomized clinical trials were taken into account, and six of them proved lack of effect of emollients in the prevention of atopic dermatitis among neonates from AD risk groups. Conclusions: Emollient treatment has a good safety profile and most of the ingredients used in formulations are nonirritant for sensitive newborn and infant skin. There is some evidence of the positive effects of emollient treatment in prevention of AD in predisposed populations. The relatively high cost of emollient treatment (vs regular infant skin-care routine) would support the necessity for further evaluation of their effectiveness in nonpredisposed populations.

Anti-Inflammatory Effect of Fermented Cabbage Extract Containing Nitric Oxide Metabolites with Silica.

The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in the ear after DNFB sensitization on the dorsal skin of mice. FCS alleviated the severity of atopic dermatitis-like skin lesions. In addition, epidermis thickness of the ear and penetration of inflammatory cells in atopic dermatitis-like skin lesions were decreased after topical application of FCS. The serum levels of TNF-α and IL-4 were measured in atopic dermatitis mice using ELISA kits, which were observed to be significantly decreased after topical application of FCS. This study demonstrates that the FCS can be used as a potential therapeutic for the treatment and prevention of AD.

Lacticaseibacillus rhamnosus and breastmilk are associated with a decreased risk of atopic dermatitis in very low birth weight premature infants.

In this study, we analyse the influence of nutrition during the early neonatal period on the development and prevention of atopic dermatitis (AD) in children with a history of very low birth weight (VLBW). A retrospective cohort study was performed of VLBW preterm infants to assess the risk of their developing AD during childhood, according to nutrition with breastmilk and/or probiotic supplementation during the neonatal period. The analysis focused on nutritional and early childhood follow-up data for 437 newborns, of whom 184 received probiotics up to 36 weeks postmenstrual age. AD was present in 23.5% of the study sample. Of the children who did not develop AD, 44.9% had received probiotics from birth to 36 weeks of gestational age. Therefore, the administration of probiotics to infants at less than 36 weeks postmenstrual age is associated with a protective effect against the development of AD (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.34-0.93). Moreover, a protective interaction was observed between probiotic administration and breastmilk (OR 0.46; 95% CI 0.25-0.82). The adjusted data in the regression model allow us to observe a statistically significant association with the protective effect of Lacticaseibacillus rhamnosus with the development of AD at school age (OR 0.55; 95% CI 0.30-0.99). Probiotic supplementation in VLBW newborns is associated with a decreased risk of subsequent development of AD. Breastmilk strengthens the protective effect of probiotics against the development of AD.

Anti-Atopic Dermatitis Effect of TPS240, a Novel Therapeutic Peptide, via Suppression of NF-κB and STAT3 Activation

Atopic dermatitis (AD) is a relapsing skin disease with persistent inflammation as a causal factor for symptoms and disease progression. Current therapies provide only temporary relief and require long-term usage accompanied by side effects due to persistent relapses. A short peptide, TPS240, has been tested for its potential to subside AD. In this study, we confirmed the anti-atopic effect of TPS240 in vivo and in vitro using a DNCB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells. In the AD mouse model, topical treatment with TPS240 diminished AD-like skin lesions and symptoms such as epidermal thickening and mast cell infiltration induced by DNCB, similar to the existing treatment, dexamethasone (Dex). Furthermore, skin atrophy, weight loss, and abnormal organ weight changes observed in the Dex-treated group were not detected in the TPS240-treated group. In TNF-α/IFN-γ-stimulated HaCaT cells, TPS240 reduced the expression of the inflammatory chemokines CCL17 and CCL22 and the pruritic cytokines TSLP and IL-31 by inhibiting NF-κB and STAT3 activation. These results suggest that TPS240 has an anti-atopic effect through immunomodulation of AD-specific cytokines and chemokines and can be used as a candidate drug for the prevention and treatment of AD that can solve the safety problems of existing treatments.

Frequency of newborn bathing in the first 9 weeks of life and related factors: An observational study in a community-based sample from Meta-LARC.

Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequency and associated factors within the first 9 weeks of life. Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta-network Learning and Research Center (Meta-LARC) practice-based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross-sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards-stepwise method and estimates from the reduced model are reported in the text. Moisturizer use (OR = 2.03, 95% CI: 1.54-2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42-2.72), a parental education level lower than a 4-year college degree (OR = 2.48, 95% CI: 1.70-3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53-2.93 and 1.04-2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01-1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52-0.87) was significantly associated with less frequent bathing. We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies.

Maternal supplementation with Limosilactobacillus reuteri FN041 for preventing infants with atopic dermatitis: study protocol for a randomized controlled trial.

Atopic dermatitis (AD) has increased rapidly with rapid urbanization; however, the treatment options for AD are lacking because the commonly used therapies can only alleviate symptoms. Limosilactobacillus reuteri (L. reuteri), FN041 is a specific strain isolated from human breast milk, and its protective potential against AD has been confirmed. This study aims to assess the efficacy of maternal consumption of L. reuteri FN041 during late pregnancy and lactation in preventing infantile AD. First, a randomized, double-blind, placebo-controlled intervention study will be conducted on 340 pregnant females with babies at high risk for AD. These subjects will be randomly divided into four groups of different doses of L. reuteri FN041 (1 × 109, 5 × 109, and 1 × 1010 CFU/d) along with a placebo. The safety and efficacy of maternal use of L. reuteri FN041 for preventing infantile AD will be analyzed, and the most efficient dosage of L. reuteri FN041 will be determined. Subsequently, a multicenter cohort study of 500 pregnant females with babies at high risk for AD will be conducted to promote the maternal application of L. reuteri FN041. These subjects will be administered L. reuteri FN041 at the optimal dose determined during the first stage of late pregnancy and lactation, and their babies will be analyzed for AD development. Recruitment was initiated in October 2022. The primary outcome is the cumulative incidence of AD at 24 months after maternal consumption of L. reuteri FN041 during late pregnancy and lactation, whereas the secondary outcome is the efficiency of L. reuteri FN041 transfer from the mother's gut to breast milk and then the infant's gut after oral supplementation. This study will demonstrate the efficacy of edible probiotics isolated from breast milk in preventing or treating AD in infants. Accordingly, we provide population-based advice for administering specific probiotics for the primary prevention of AD in pregnant females. Understanding the underlying mechanisms of probiotic strains derived from breast milk can promote their application in preventing infant diseases associated with intestinal microbiota imbalance and immune disorders. https://www.chictr.org.cn/, identifier [ChiCTR2300075611].

Low-Density Lipoprotein Cholesterol Is Associated with Atopic Dermatitis in Korean Adolescents

Introduction: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Several studies have investigated the relationship between obesity and AD prevalence, but the results have been conflicting. This study investigated the association between obesity and AD in Korean adolescents. Methods: We used nationally representative data regarding 1,617 Korean adolescents aged 12–18 years, which were obtained from the cross-sectional Korea National Health and Nutrition Examination Survey 2017–2019. Multiple logistic regression analysis (including age, sex, region of residence, number of household members, economic status, lipid profile, and stress level) was used to evaluate the relationships of obesity and abdominal obesity with doctor-diagnosed AD. Results: Although the results were not statistically significant, obese adolescents were diagnosed with AD (20.8%) more often than non-obese adolescents (20.8% vs. 14.5%, p = 0.055). This tendency was more prominent in male adolescents than in female adolescents, but the finding was not statistically significant. Body mass index and the prevalence of abdominal obesity did not differ between the AD and non-AD groups. Adolescents with AD had significantly higher total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, compared with adolescents who did not have AD. In the adjusted model, an LDL-C level ≥130 mg/dL was a risk factor for AD (adjusted odds ratio, 1.03; 95% confidence interval, 1.01–1.05). Conclusions: A high LDL-C level may be a risk factor for AD. Proper management of dyslipidemia through lifestyle modification may aid in AD prevention and control. Further large-scale prospective studies are needed to assess the associations of AD with obesity and dyslipidemia.

Atopic dermatitis and risk of 14 site-specific cancers: A Mendelian randomization study.

Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk. To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study. From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (p < 5 × 10-8 ) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses. We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini-Hochberg correction, the inverse-variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94-1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92-1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers. Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.

Systemic inflammatory proteins in offspring following maternal probiotic supplementation for atopic dermatitis prevention

BackgroundMaternal probiotic supplementation has a promising effect on atopic dermatitis (AD) prevention in infancy. In the randomised controlled study, Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT), maternal probiotics reduced the cumulative incidence of AD in their offspring by 40% at 2 years of age. However, our understanding on how probiotics prevented AD is still limited, and the role of inflammatory proteins in infants following maternal probiotic supplementation is unclear. We hypothesised that maternal probiotics lowered pro-inflammatory proteins and increased anti-inflammatory proteins in their 2-year-old children as a mechanism of AD prevention. We aimed to explore this hypothesis and the association between these proteins and the presence of AD, severity of AD, and the degree of preventive effect of probiotics.MethodsPlasma samples were collected from 2-year-old children (n = 202) during the ProPACT study, a randomised placebo-controlled trial of maternal probiotic supplementation. These samples were analysed for 92 inflammatory proteins using a multiplex proximity extension assay. Associations between inflammatory proteins and the presence and severity of AD, and the degree of preventive effect, was estimated individually using regression analysis and then collectively using unsupervised cluster analysis.ResultsSeveral proteins were observed to differ between the groups. The probiotic group had lower CCL11 and IL-17C, while children with AD had higher IL-17C, MCP-4, uPA, and CD6. Cytokine CCL20 and IL-18 had moderate correlation (r = 0.35 and r = 0.46) with the severity of AD. The cluster analysis revealed that children in the cluster of samples with the highest value of immune checkpoint receptors and inflammatory suppressor enzymes showed the greatest AD preventive effect from probiotics.ConclusionsThe proteins associated with both maternal probiotic supplementation and the presence and severity of AD warrant attention because of their potential biological relevance. Cluster analysis may provide a new insight when considering which subgroups benefit from probiotic supplementation. Larger studies are needed to confirm the results.Trial registration number: The study was retrospectively registered at ClinicalTrials.gov (NCT00159523) on 12nd September 2005.

Meta-analysis on preventive and therapeutic effects of probiotic supplementation in infant atopic dermatitis.

Despite a large body of research, the effect of probiotic administration on the incidence and severity of atopic dermatitis (AD) shows conflicting results. We aimed to investigate whether probiotic supplementation reduces the incidence and severity of AD. Three databases were systematically searched. A 22% lower incidence of AD was found in the probiotic group. The reduction in incidence was 49% when probiotics were given to pregnant and lactating mothers, and 27% when they were given to pregnant mothers and infants. A 39% reduction of AD incidence was achieved when administered to pregnant-breastfeeding mothers and infants. Significant differences in SCORAD (SCORing Atopic Dermatitis) favoring probiotics were observed, but the IDLQI remained unchanged. Lactobacillus (L.) rhamnosus was the most documented strain, but it turned out to be ineffective in reducing SCORAD. Conversely, L. paracasei and L. sakei showed a significant decrease in SCORAD. Probiotics are effective in the prevention of AD, but the effect is less conclusive for the treatment of AD, especially in infants <1year. The intake of probiotics by breastfeeding mothers is an important measure and may become a novel preventive strategy. The preventive effect of probiotics against AD is not associated with family background or AD risk. L. paracasei and L. sakei show the greatest reduction in SCORAD.

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes

BackgroundAn association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches.MethodsPublic genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package ‘TwoSampleMR’ was used for analysis.ResultsGenetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34; P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11; P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran’s Q test and I2 statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium.ConclusionGenetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.

Parnassin, a Novel Therapeutic Peptide, Alleviates Skin Lesions in a DNCB-Induced Atopic Dermatitis Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory skin disease which requires continuous treatment due to its relapsing nature. The current treatment includes steroids and nonsteroidal agents targeting inflammation but long-term administration causes various side effects such as skin atrophy, hirsutism, hypertension and diarrhea. Thus, there is an unmet need for safer and effective therapeutic agents in the treatment of AD. Peptides are small biomolecule drugs which are highly potent and remarkably have less side effects. Parnassin is a tetrapeptide with predicted anti-microbial activity curated from Parnassius bremeri transcriptome data. In this study, we confirmed the effect of parnassin on AD using a DNCB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells. In the AD mouse model, topical administration of parnassin improved skin lesions and symptoms in AD mice, such as epidermal thickening and mast cell infiltration, similar to the existing treatment, dexamethasone, and did not affect body weight, or the size and weight of spleen. In TNF-α/IFN-γ-stimulated HaCaT cells, parnassin inhibited the expression of Th2-type chemokine CCL17 and CCL22 genes by suppressing JAK2 and p38 MAPK signaling kinases and their downstream transcription factor STAT1. Parnassin also significantly reduced the gene expression of TSLP and IL-31, which are pruritus-inducing cytokines. These findings suggested that parnassin alleviates AD-like lesions via its immunomodulatory effects and can be used as a candidate drug for the prevention and treatment of AD because it is safer than existing treatments.

The effect of probiotics in the prevention of atopic dermatitis in children: a systematic review and meta-analysis.

Probiotics have anti-inflammatory effects and can alleviate clinical symptoms of atopic dermatitis (AD) in children. However, the effects of probiotics on AD in children were controversial. This study aimed to evaluate the clinical efficacy of probiotics in the prevention of AD in children by a meta-analysis method. Randomized controlled trials (RCTs) on probiotics in the prevention of AD in children performed at home and abroad were searched in the PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases using a combination of subject terms and free terms. The retrieval time was from the establishment of the database to November 2022. Meta-analysis was performed by using Stata 14.0 software. The inclusion criteria were based on the Population, Intervention, Comparison, Outcomes and Study (PICOS) framework. (I) Participants: age ≤18; (II) Intervention: the intervention group received probiotics; (III) Control: the control group received placebo; (IV) Outcomes: AD; (V) the type of study: randomized control group. We collected the number of two groups and the number of AD in the included literatures. The I2 statistic was employed to evaluate heterogeneity. Thirty-seven RCTs were eventually included, including 2,986 in the experimental group and 3,145 in the control group. The meta-analysis showed that probiotics were superior to placebo in the prevention of AD [risk ratio (RR) (95% confidence interval): 0.83 (0.73, 0.94), I2=65.2%]. The sub-group meta-analysis showed that the clinical efficacy of probiotics in the prevention of AD was more significant in the following groups: mothers and infants, before and after childbirth, Lactobacillus rhamnosus or mixed probiotics, follow-up time ≤2 years, and conducted in Europe. Probiotic intervention may provide an effective means of preventing AD in children. However, due to the heterogeneity of the results of this study, the results need confirmation in follow-up studies.