2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.

The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.

Allergic diseases such as asthma, eczema, and food allergies are rising globally. The infant gut microbiota, particularly the dominance of Bifidobacterium, shapes immune development and allergy risk. In Japan-where Bifidobacterium prevalence is notably high-longitudinal investigations focusing on the pre-weaning period, when external influences are relatively limited, remain scarce. Therefore, based on consistent hypotheses and findings from previous studies, we investigated how two important early factors-antibiotic exposure at birth and the presence of older siblings-influence the gut environment in early infancy and subsequent allergy development.

In a prospective cohort of 121 Japanese infants, stool samples were collected at seven time points from birth through 24 months. We quantified the relative abundances of Bifidobacterium, Bacteroides, Clostridium, and Faecalibacterium and recorded allergic outcomes at 2 years. Both antimicrobial exposure at delivery and sibling presence significantly altered gut microbiota composition and overall diversity in early infancy. Although the full cohort showed no consistent diversity or Bifidobacterium differences by allergic status, in several subgroups where these two factors were excluded, infants who had an allergy by 24 months exhibited marked shifts in early gut microbiota community structure-particularly in beta diversity-and reduced Bifidobacterium occupancy during the pre-weaning period (1-6 months) versus non-allergic peers. Moreover, infants whose gut microbiota was initially affected by these factors showed a recovery in diversity after weaning, a rebound more pronounced in non-allergic individuals.

These findings indicate that both the initial community configuration and its capacity to rebound after perturbation are critical determinants of allergy risk. By focusing on dynamic changes through weaning and adjusting for decisive confounders, this study refines insight beyond prior cross-sectional work. Early interventions that preserve or restore microbial diversity and Bifidobacterium dominance may therefore offer a promising strategy to mitigate allergic disease development.

Despite the different pathologies and genetic susceptibilities of childhood ALL, T1DM and allergies, these conditions share epidemiological risk factors related to timing of infectious exposures and acquisition of the gut microbiome in infancy. We have assessed whether lower microbiome diversity (Shannon Index) and shared genus/species profiles are associated with pediatric ALL, allergies, and T1DM.

Literature search was performed using PubMed, Embase, Cochrane, and Web of Science databases. Case-control, meta-analyses, and cohort studies were considered for inclusion. Inclusion criteria: (i) subjects age 1-18 years at diagnosis, (ii) reports effect of microbiome measured prior to/at time of diagnosis/first intervention (iii) outcome of ALL, allergies, asthma, or T1DM, (iv) English text. Exclusion criteria: (i) age < 1 or >18 years at diagnosis, (ii) Down Syndrome-associated ALL, (iii) non-English text, (iv) reviews, pre-print, or abstracts, (v) heavily biased studies. Abstract and full text screening were performed by two independent reviewers. Data extraction was performed by one reviewer following PRISMA guidelines. Data were pooled using a random-effects model. Eighty-eight studies were included in the analysis, with seventy-seven in the qualitative analysis and 54 in the meta-analysis. Cases were found to have lower alpha-diversity than controls in ALL (SMD:-0.78, 95%CI:-1.21, -0.34), T1DM (SMD:-1.26, 95%CI:-3.49, 0.96), eczema (SMD:-0.34, 95%CI:-0.56, -0.12), atopy (SMD:-0.06, 95%CI:-0.34, 0.22), asthma (SMD:-0.37, 95%CI:-1.16, 0.42), and food allergy (SMD:-0.11, 95%CI:-0.63, 0.41).

These results highlight similarities in the microbiome diversity and composition of children with ALL, T1DM, and allergies. This is compatible with a common risk factor related to immune priming in infancy and highlights the gut microbiome as a potentially modifiable risk factor and preventative strategy for these childhood diseases.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).

In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.

Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.

FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

In modern urbanized societies, the incidence of major immune-mediated diseases is several times higher than before World War II. A potential explanation is that these diseases are triggered by limited possibilities to be exposed to rich environmental microbiota. This requires that the urban environment hosts less and poorer microbiota than the natural environment. The current study was designed to test the assumption that urban man-made environments host less and poorer environmental microbiota, compared to natural habitats. We selected two types of dry environments, natural rocks and playground rubber mats, both of which were used daily and extensively by children. In quantitative PCR and next-generation sequencing, bacterial abundance and richness were higher on the natural rocks than the rubber mats. Altogether, 67 amplicon sequence variants (ASVs) belonging mostly to Actinobacteria and Proteobacteria were indicative of rock microbiota, while three ASVs were indicative of rubber mats. Interestingly, bacteria formed more complex networks on rubber mats than natural rocks. Based on the literature, this indicates that the studied artificial dry environment is more challenging and stressful for bacterial communities than dry natural rocks. The results support the hypothesis that urban man-made environments host poor microbial communities, which is in accordance with the biodiversity hypothesis of immune-mediated diseases.IMPORTANCEThe current study provides new evidence that artificial urban play environments host poor microbial communities and provide a stressful environment for microbes, as compared to dry natural rocks. Through this, the current study underlines the need to enhance microbial diversity in urban areas, especially in outdoor play environments, which have a crucial role in providing essential microbial exposure for the development of children's immune system. This research can potentially offer guidance for urban planning and public health strategies that support planetary health.

We hypothesized that food sensitization in children could be linked to specific gut microbiota. The objective of this study is to assess a group of children with egg white sensitization (ES) from the microbiological and biochemical-metabolic standpoint, applying the microbiota and metabolomics approach to studying the intestinal contents of the feces.

Twenty-eight toddlers with ES (mean age 13.08 months) and 24 healthy controls (mean age 12.85 months) were recruited for feces collection, serum IgE measurement, gut microbiota and metabolomics analysis. Individual microbial diversity and composition were analyzed via targeting the 16S rRNA gene hypervariable V3-V5 regions. The metabolite profiles of human feces were explored by 1 H nuclear magnetic resonance.

Children with ES exhibited relatively high levels of Firmicutes at the phylum level and relatively low levels of Bacteroidetes. Moreover, children with ES exhibited significantly reduced overall gut microbiota diversity and richness compared with healthy children. At the family level, we observed significant increases in the numbers of Clostridiaceae, Lachnospiraceae, Pasteurellaceae and Ruminococcaceae in children with ES. Egg white sensitivity increases orotic acid, nicotinate, methyl succinate, urocanic acid, xanthine, amino acids (tyrosine, lysine, tryptophan, phenylalanine) and short-chain fatty acids ( n -butyrate, valerate) levels according to the results of metabolomics analysis.

In summary, some specific families and genera (dysbiosis) are enriched in the gut microbiota, and increases in the mean concentrations of organic compounds in the fecal metabolite profile are associated with ES in children. These findings may provide evidence of potential strategies to control the development of ES or other atopies by modifying the gut microbiota.

Background: The role of gut dysbiosis in the pathophysiology of atopic dermatitis (AD) through immune system (IS) imbalance is a novel line of investigation currently under discussion. This study aimed to characterize compare the composition and functional profile of the gut microbiota (GM) between adults with AD and healthy individuals. Methods: Observational cross-sectional study, where fecal samples from 70 adults (38 patients and 32 controls) were analyzed using metagenomics and bioinformatics. Results: Differences between the GM of patients with AD and healthy individuals were demonstrated. Reduced microbial diversity was found in subjects with AD. Bacterial species with lower abundance primarily belonged to the families Ruminococcaceae, Akkermansiaceae, and Methanobacteriaceae. Several microbial metabolic pathways were found to be decreased in patients with AD, including amino acid biosynthesis, vitamin biosynthesis, fatty acids and lipids biosynthesis, and energy metabolism. Conclusion: Adults with AD exhibited a distinct GM compared to healthy individuals. Changes were demonstrated both compositionally and functionally. Further investigation is mandatory to elucidate the potential link and causal relationship between gut dysbiosis and AD, which may be crucial for a deeper understanding of the disease's pathophysiology and the development of novel therapeutic approaches.

Epidemiological studies indicate a rising prevalence of allergic diseases, now recognized as a major global public health concern. In children, the progression of these diseases often follows the "atopic march," beginning with eczema, followed by food allergies, allergic rhinitis, and asthma. Recent research has linked gut microbiota dysbiosis to the development of allergic diseases in children. The gut microbiota, a crucial component of human health, plays a vital role in maintaining overall well-being, highlighting its potential in preventing and modifying the course of allergic diseases. This review examines the relationship between childhood allergic diseases and gut microbiota, drawing on the latest evidence. We first elaborated the concepts of allergic diseases and gut microbiota, followed by a discussion of the developmental trajectory of the gut microbiota in healthy children. This review further explored the richness, diversity, and composition of the gut microbiota, as well as specific microbial taxa associated with allergic disease. Lastly, we discussed the current status and future potential of probiotic interventions in managing pediatric allergic diseases.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the appearance of recurrent eczematous lesions and intense itching. The World Allergy Organization (WAO) suggested the administration of probiotics in pregnant women at high risk of allergies in their children.

Our study aims to evaluate the role of administering the Bifidobacterium bifidum strain PRL2010 during pregnancy and breastfeeding in preventing and/or reducing the severity of AD manifestations in children.

It is a monocentric, randomized, double-blind, placebo-controlled trial with probiotic/placebo administration since the 36th week of gestation to mothers with atopy or a family history of atopy; the effects were evaluated over the first 12 months of the children's lives.

No severe adverse effects due to probiotic intake were reported in our cohort. Although proportionally fewer children with AD were in the probiotic group, the statistical analysis showed no significant differences between the probiotic and placebo groups. However, infants who developed the most severe forms of AD in the probiotic group showed a better clinical course during follow-up compared to those in the placebo group.

In conclusion, administering the probiotic Bifidobacterium bifidum strain PRL2010 during pregnancy and breastfeeding is safe and potentially beneficial; further large-scale studies may confirm its usefulness in improving the clinical manifestation of AD in children with a family history of atopy.

The interplay between human health and the microbiome has gained extensive attention, with probiotics emerging as pivotal therapeutic agents due to their vast potential in treating various health issues. As significant modulators of the gut microbiota, probiotics are crucial in maintaining intestinal homeostasis and enhancing the synthesis of short-chain fatty acids. Despite extensive research over the past decades, there remains an urgent need for a comprehensive and detailed review that encapsulates probiotics' latest insights and applications. This review focusses on the multifaceted roles of probiotics in promoting health and preventing disease, highlighting the complex mechanisms through which these beneficial bacteria influence both gut flora and the human body at large. This paper also explores probiotics' neurological and gastrointestinal applications, focussing on their significant impact on the gut-brain axis and their therapeutic potential in a broad spectrum of pathological conditions. Current innovations in probiotic formulations, mainly focusing on integrating genomics and biotechnological advancements, have also been comprehensively discussed herein. This paper also critically examines the regulatory landscape that governs probiotic use, ensuring safety and efficacy in clinical and dietary settings. By presenting a comprehensive overview of recent studies and emerging trends, this review aims to illuminate probiotics' extensive therapeutic capabilities, leading to future research and clinical applications. However, besides extensive research, further advanced explorations into probiotic interactions and mechanisms will be essential for developing more targeted and effective therapeutic strategies, potentially revolutionizing health care practices for consumers.

Epidemiological studies have associated reduced bacterial diversity and abundance and food allergy. This mechanistic review investigated the link between gut dysbiosis and food allergy with a focus on the role of short-chain fatty acids (SCFAs) in modulating T-cells. T-cell differentiation poses an opportunity to direct the immune cells towards an anergic regulatory T cell (Treg) or allergic T helper 2 (Th2) response. Probiotic intervention to prevent and/or treat atopic disease symptoms through this mechanistic pathway was explored.

A narrative review was conducted following a three-stage systematic literature search of EMBASE and Medline databases. Ninety-six of 571 papers were accepted and critically appraised using ARRIVE and SIGN50 forms. Thematic analysis identified key pathophysiological mechanisms within the narrative of included papers.

Preclinical studies provided compelling evidence for SCFAs' modulation of T-cell differentiation, which may act through G-protein coupled receptors 41, 43 and 109a and histone deacetylase inhibition. Foxp3 transcription factor was implicated in the upregulation of Tregs. Human probiotic intervention studies aimed at increasing SCFAs and Tregs and preventing atopic disease showed inconclusive results. However, evidence for probiotic intervention in children with cow's milk protein allergy (CMPA) was more promising and warrants further investigation.

Preclinical evidence suggests that the mechanism of gut dysbiosis and reduced SCFAs may skew T-cell differentiation towards a Th2 response, thus inducing allergy symptoms. Probiotic trials were inconclusive: probiotics were predominantly unsuccessful in the prevention of allergic disease, however, may be able to modulate food allergy symptoms in infants with CMPA.

Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child's life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: "the impact of intestinal microbiota on the development of immune diseases and asthma", "intestinal microbiota and allergic diseases", "the impact of intrauterine microbiota on the development of asthma", "intrauterine microbiota and immune diseases", "intrauterine microbiota and atopic dermatitis", "intrauterine microbiota and food allergies", "maternal microbiota", "fetal microbiota" and "neonatal microbiota". The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect.

Many studies reported the influence of infants' gut microbiota on atopic dermatitis (AD) postnatally, yet the role of maternal gut microbiota and plasma metabolites in infants' AD remains largely unexplored.

Sixty-three pregnant mother-infants were enrolled and followed after childbirth in Guangzhou, China. Demographic information, maternal stool and plasma samples, and records for infants' AD were collected. Maternal gut microbiota/metabolome and plasma metabolome were profiled using shotgun metagenomics and non-targeted metabolomics. Logistic regression and multi-omics analysis were used to explore characteristic maternal gut microbiota in the AD and health groups.

The α-diversity of maternal gut microbiota in health group was significantly higher than AD group (Shannon diversity P = 0.02, Simpson diversity P = 0.04). Short-chain fatty acids (SCFAs) producing microorganisms, including Faecalibacterium, Roseburia, Butyricicoccus, and Ruminococcus, as well as the abundance of phenylalanine, tyrosine, and tryptophan biosynthesis pathway, were enriched in health group (LDA>2 and P < 0.05). Virulent factors (VFs) involved in immune modulation were enriched in the health group, while VFs involving in adhesin were enriched in the AD group (P < 0.05). Metabolomic analysis showed that a polyunsaturated fatty acid/linoleic acid, 13S-hydroxyoctadecadienoic, were negatively associated with AD in both the gut and plasma samples (FDR<0.05). Several other linoleic acids and flavonoids were negatively associated with AD (FDR<0.05). Neural network analysis revealed that microorganisms enriched in health group may produce these protective fatty acids.

Our findings show that maternal gut microorganisms/metabolites and plasma metabolites during pregnancy impact subsequent pathogenesis of infants AD. This illuminates new strategies against early AD in offspring.

Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases.

We sought to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk.

We undertook a double-blind randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2 g daily of galacto-oligosaccharides and fructo-oligosaccharides in the ratio 9:1) or placebo (8.7 g daily of maltodextrin) powder from less than 21 weeks' gestation until 6 months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was medically diagnosed infant eczema by age 1 year, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by age 1 year.

A total of 652 women were randomized between June 2016 and November 2021 (329 in the prebiotics group and 323 in the placebo group). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by age 1 year (prebiotics 31.5% [103 of 327 infants] vs placebo 32.6% [105 of 322 infants]; adjusted relative risk, 0.98; 95% CI, 0.77-1.23; P = .84). Secondary outcomes and safety measures also did not significantly differ between groups.

We found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of medically diagnosed infant eczema by age 1 year in infants who are at hereditary risk of allergic disease.

Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field.

Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field.

Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes.

We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.

Background: Balanced diversity and abundance of gut microbiome play important roles in human health, including neonatal health. Though not established, there is evidence that the delivery route could alter the diversity of neonatal gut microbiomes. Objective: The objective of the study was to investigate the differences in the gut microbiomes of neonates delivered via cesarean section compared to those born by vaginal delivery and to identify the predominant microbial taxa present in each group. Study Design: A prospective observational study of 281 healthy neonates born between February 2021 and April 2023 at Her Royal Highness Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Thailand, was performed. The study population was divided into two groups: 139 neonates born via vaginal delivery and 141 neonates born via cesarean section. The microbiota composition of each neonate's fecal sample was identified by using 16S ribosomal ribonucleic acid metagenomic sequencing. Results: Neonates delivered vaginally exhibited a gut microbiome with higher abundance and diversity than those delivered by cesarean delivery. Bifidobacterium was the dominant genus in both groups. Bifidobacterium breve was the dominant species and was significantly higher in cesarean-delivered neonates compared to those delivered vaginally (24.0% and 9.2%, respectively) (p < 0.001). However, the taxonomy of only 89 (64.0%) and 44 (31.43%) fecal samples could be identified from the vaginal and cesarean delivery groups, respectively. Conclusion: Route of delivery is associated with neonatal gut microbiome abundance and diversity. Neonates delivered via vaginal delivery exhibited higher diversity but lower abundance of the dominant species in the gut microbiome. Trial Registration: Thai Clinical Trials Registry identifier: TCTR20221024003.

Children growing up on farms or with pets have a lower risk of developing allergy, which may be linked to their gut microbiota development during infancy.

Children from the FARMFLORA birth cohort (N = 65), of whom 28 (43%) lived on a dairy farm and 40 (62%) had pets, provided fecal samples at intervals from 3 days to 18 months of age. Gut microbiota composition was characterized using quantitative microbial culture of various typical anaerobic and facultatively anaerobic bacteria, with colonization rate and population counts of bacterial groups determined at the genus or species level. Allergy was diagnosed at three and eight years of age by experienced pediatricians. Generalized estimating equations were used to identify associations between farm residence or pet ownership, gut microbiota development and allergy. Adjustments were made for important potential confounders.

Growing up on a farm was associated with a higher ratio of anaerobic to facultative bacteria in the first week, smaller Escherichia coli populations in colonized children in the first months of life and less frequent colonization by Clostridioides difficile at 12 months of age. Having pets in the household was associated with more frequent colonization by Bifidobacterium, Lactobacillus and Bacteroides in the first months. A higher ratio of anaerobic to facultative bacteria at one week of age, early colonization by Bifidobacterium, Lactobacillus and Bacteroides, and reduced carriage of C. difficile at 4-12 months of age all correlated negatively with subsequent allergy diagnosis.

Our findings indicate that lower rates of allergy in children growing up on farms or with pets may be related to early establishment of typical anaerobic commensals in their gut microbiota. However, further studies are needed to validate our observations in this small birth cohort study.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

Recent studies have demonstrated the anti-allergic effects of probiotics in humans. However, their role in preventing and treating pediatric allergic rhinitis has not been thoroughly investigated. This study aimed to systematically review the efficacy and preventive effects of probiotics on pediatric allergic rhinitis.

We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases for all relevant studies on probiotics and pediatric allergic rhinitis. Studies meeting the inclusion criteria were included, data were extracted, and meta-analyses were performed.

A total of 28 studies with 4,765 participants were included in this study. The pooled results showed that the use of probiotics was associated with a significant improvement in total nose symptom scores (SMD, -2.27; 95% CI, -3.26 to -1.29; P < 0.00001), itchy nose scores (SMD, -0.44; 95% CI, -0.80 to -0.07; P = 0.02), sneezing scores (SMD, -0.47; 95% CI, -0.84 to -0.10; P = 0.01), eye symptoms (SMD, -3.77; 95% CI, -5.47 to -2.07; P < 0.00001), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (SMD, -2.52; 95% CI, -4.12 to -0.92; P < 00001). However, the use of probiotics was not associated with the incidence of allergic rhinitis (RR, 0.9; 95% CI, 0.74-1.08; P = 0.26).

The present study demonstrated that probiotics were effective and safe for improving pediatric allergic rhinitis symptoms and quality of life. However, probiotics could not prevent pediatric allergic rhinitis.

The connection between the immune response and the composition of gut microbiota has been associated with an increased prevalence of atopic dermatitis in the first year of life. The study aimed to investigate gut microbiota characteristics in infants with atopic dermatitis compared to healthy infants to better understand the link between early-life microbiota composition and the development of atopic dermatitis. The study analyzed the intestinal microbiota of 121 infants with clinical signs of atopic dermatitis, divided into Group I (infants with atopic dermatitis) and Group II (healthy controls). The study showed that infants with atopic dermatitis presented increased values of proteolytic bacteria mainly represented by Enterobacter species (P = 0.041), Klebsiella species (P = 0.038), and Escherichia coli (P = 0.013), with significantly decreased levels of acidifying bacteria represented by Enterococcus species, Lactobacillus and Bifidobacterium (P < 0.05) and normal levels of Clostridium species, Candida albicans, Mould fungi and Geotrichum species. This study highlights distinct differences in the gut microbiota of infants with atopic dermatitis, providing insights into the dynamic intestinal ecosystem during early life for future personalized therapeutic strategies.

The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".

Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.

Atopic dermatitis (AD) is a chronic inflammatory skin condition affecting a significant portion of the population, with prevalence rates of 25% in children and 7-10% in adults. AD not only poses physical challenges but also profoundly impacts patients' mental well-being and quality of life. The stability of gut microbiota is crucial for overall health and can influence AD progression by modulating immune function, skin barrier integrity, and neuroendocrine signaling, which may be an effective target for the prevention and treatment of AD. Thus, exploring the interactions between AD and gut microbiota, particularly in infants, can provide insights into potential preventive and therapeutic strategies. This study aimed to explore the correlation between AD and gut microbiota while providing an overview of current research trends and emerging areas of interest in this field.

A comprehensive search was conducted on the Web of Science Core Collection (WOSCC) for relevant publications from January 1, 2014, to December 31, 2023. English-language articles and reviews were included. Two investigators independently screened the publications, and visual analysis was performed using CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel software.

A total of 804 articles were included, showing a significant increase in publications over the past decade. The United States, Wageningen University, and University Ulsan (represented by Hong SJ) had the highest number of published papers. Nutrients was the journal with the most publications, while the Journal of Allergy and Clinical Immunology had the highest number of citations and centrality among co-cited journals. Keyword visualization analysis identified "atopic dermatitis" and "gut microbiota" as central themes. Notably, there has been a notable shift in research focus over the years, with early studies concentrating on "Fecal microbiota," "caesarean section," and "first 6 months," while recent studies have highlighted the roles of "cells," "dysbiosis," and "prebiotics." This shift indicates growing interest in the underlying mechanisms and potential therapeutic interventions related to the intestinal microecology in AD treatment.

The field of AD and gut microbiota research has evolved significantly, with an increasing focus on understanding the intricate interactions between gut microbiota and AD pathogenesis. Recent years have witnessed increased interest in understanding the relationship between AD and gut microbiota, with researchers conducting extensive studies exploring various aspects of this connection. This review analyzes research trends over the past decade, highlighting trends and hotspots in the study of AD, particularly in infants, and the role of microbiota. This review serves as a valuable reference for future investigations, aiming to provide deeper insights into this burgeoning field and suggests directions for future research.

The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD.

From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS.

In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings.

Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms.

Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life.

Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care.

Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.

Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms.

To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies.

Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI.

Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-γ) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions.

This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis.

Previous studies have indicated a controversy regarding the association between dietary micronutrient concentrations and the risk of allergic diseases. In this study, we employed Mendelian randomization (MR) analysis using data from two samples to investigate the causal relationship between circulating micronutrient concentrations and three allergic diseases.

In this study, we considered 16 circulating micronutrients as exposure variables (beta carotene, calcium, copper, folate, iron, lycopene, magnesium, phosphorus, selenium, vitamin A1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and zinc); and three common allergic diseases (allergic asthma [AA], atopic dermatitis [AD], and allergic rhinitis [AR]) as outcomes. The inverse variance weighted (IVW) method was primarily applied for MR analysis, supplemented by MR-Egger and weighted-median methods to corroborate the IVW results; and sensitivity analysis was conducted to ensure the robustness of the MR assumptions.

Our results revealed that an increase in serum phosphorus and zinc concentrations may diminish the risk of AA, while for AD an increase in serum zinc concentration may reduce the risk, but an increase in serum vitamin C concentration may elevate the risk. As for AR, an increase in serum phosphorus and selenium concentrations appeared to be associated with a reduced risk. We did not find evidence for an association between other micronutrients and the risk of allergic diseases.

Our study indicates that an increase in serum phosphorus and zinc concentrations may reduce the risk of AA, while an increase in serum zinc concentration may reduce the risk of AD, but an increase in serum vitamin C concentration may elevate the risk of AD. An increase in serum phosphorus and selenium concentrations is associated with a reduced risk of AR. This provides additional support for research on the effects of micronutrients on allergic diseases.

The gut microbiota is closely related to infant health. However, the impact of environmental factors on the gut microbiota has not been widely investigated, particularly in vulnerable populations such as infants admitted to the neonatal intensive care unit (NICU). This study investigated the association between exposure to 12 metals and the composition of the gut microbiota in infants admitted to the NICU. Metal concentrations were determined in serum samples obtained from 107 infants admitted to the NICU at Hunan Children's hospital, China. Gut microbiota data were derived from 16S rRNA sequencing using stool samples. Generalized linear regression (GLR) models and Bayesian kernel machine regression (BKMR) analyses were used to estimate the associations between metals and both alpha-diversity indices and bacterial taxa. The GLR models showed that tin correlated negatively with the Shannon index (β = -0.55, 95% conficence interval [CI]: -0.79, -0.30, PFDR< 0.001) and positively with the Simpson index (β = 0.26, 95% CI: 0.13, 0.39, PFDR< 0.001). The BKMR analysis yielded similar results, showing that tin had the largest posterior inclusion probability for both the Shannon (0.986) and the Simpson (0.796) indices. Tin, cadmium, mercury, lead, and thallium were associated with changes in one or more taxa at the genus level. The BKMR analysis also revealed a negative correlation between metal mixtures and Clostridium_sensu_stricto, and tin contibuted mostly to the negative correlation. Early postnatal exposure to metals were associated with differences in the microbiome among infants admitted to the NICU. However, as the study was cross-sectional, these relationships must be confirmed in further studies.

The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a TH2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy.

Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome and immune system maturation. As a result, breastfeeding can impact infant health from infancy, through adolescence, and into adulthood. From protecting the infant from infections, to reducing the risk of obesity, type 1 diabetes and childhood leukaemia, many positive health outcomes are observed in infants receiving breastmilk. For the mother, breastfeeding protects against postpartum bleeding and depression, increases weight loss, and long-term lowers the risk of type 2 diabetes, breast and ovarian cancer, and cardiovascular diseases. Beyond infants and mothers, the wider society is also impacted because of avoidable costs relating to morbidity and mortality derived from a lack of human milk exposure. In this review, Medline was used to search for relevant articles to discuss the health benefits of breastfeeding and its societal impact before exploring future recommendations to enhance our understanding of the mechanisms behind breastfeeding's positive effects and promote breastfeeding on a global scale.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.

Microbial imbalance in the gut from antibiotic use may be an etiologic factor of Kawasaki disease (KD). We aimed to identify the association between the use of antibiotics and the development of KD, considering various antibiotic profiles.

A population-based, case-control study was performed using data from the Health Insurance Review and Assessment Service database. Children <5 years of age, who were diagnosed with KD between 2016 and 2019, were identified. Propensity score-matched controls were selected from the general population in a 1:5 ratio. Four separate study cohorts were created according to different periods of antibiotic use: (1) within 28 days and (2) 12 months after birth and (3) within 6 months and (4) 12 months from the index date. Profiles regarding antibiotic use were compared between patients with KD and matched controls.

We included 17,818 patients with KD and 89,090 matched controls. Use of antibiotics within 6 months [odds ratio (OR): 1.18; 95% confidence interval (CI): 1.12-1.26] and 12 months (OR: 1.23; 95% CI: 1.14-1.32) from the index date were associated with the development of KD. The association between antibiotic use and KD was most prominent in patients who had received 3 or more types of antibiotics within 12 months from the index date (OR: 1.26; 95% CI: 1.17-1.37).

Antibiotic use within the preceding 6 or 12 months was associated with KD. Alteration in gut microbiota due to antibiotic usage might play a role in the development of KD.