Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration.

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Trichinella spiralis Paramyosin Alleviates Collagen-Induced Arthritis in Mice by Modulating CD4+ T Cell Differentiation.

Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4+ T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4+ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4+ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4+ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4+ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4+ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases.

Evaluating the Toxocara cati extract as a therapeutic agent for allergic airway inflammation.

BACKGROUND: The hygiene hypothesis suggests that early life exposure to helminth infections can reduce hypersensitivity in the immune system. OBJECTIVE: The present study aims to evaluate the effects of Toxocara cati (T. cati) somatic products on allergic airway inflammation. METHODS: Between 2018 and 2020, T. cati adult worms were collected from stray cats in Mashhad, Iran (31 out of 186 cats), and their somatic extract was collected. Thirty BALB/c mice were equally divided into three groups, including the OVA group (sensitized and challenged with ovalbumin), the somatic administered group (received somatic extract along with ovalbumin sensitization), and the PBS group (sensitized and challenged with phosphate buffer saline). Bronchoalveolar lavage (BAL) fluid was collected to assess the number of cells, and lung homogenates were prepared for cytokine analysis. Histopathological analysis of the lungs was performed, and inflammatory cells and mucus were detected. Cytokine levels (IL-4, IL-5, IL-10) were measured using enzyme-linked immunosorbent assay (ELISA), and ovalbumin-specific immunoglobulin E (IgE) levels were determined using a capture ELISA. RESULTS: The somatic group significantly decreased regarding the lung pathological changes, including peribronchiolitis, perivasculitis, and eosinophil influx, compared to the group treated with ovalbumin alone. These changes were accompanied by a decrease in proinflammatory cytokines IL-4 and IL-5 and an increase in the anti-inflammatory cytokine IL-10, indicating a shift toward a more balanced immune response. The number of inflammatory cells in the BAL fluid was also significantly reduced in the somatic group, indicating a decrease in inflammation. CONCLUSION: These preclinical findings suggest that in experimental models, T. cati somatic extract exhibits promising potential as a therapeutic agent for mitigating allergic airway inflammation. Its observed effects on immune response modulation and reduction of inflammatory cell infiltration warrant further investigation in clinical studies to assess its efficacy and safety in human patients.

Urban indoor gardening enhances immune regulation and diversifies skin microbiota - A placebo-controlled double-blinded intervention study.

According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. Here we test the underlying assumption of the hygiene and biodiversity hypotheses by instructing volunteers to grow edible plants indoors during the winter season when natural exposure to environmental microbiota is low. The one-month randomized, placebo-controlled double-blind trial consisted of two treatments: participants received either microbially diverse growing medium or visually similar but microbially poor growing medium. Skin microbiota and a panel of seven immune markers were analyzed in the beginning of the trial and after one month. The diversity of five bacterial phyla (Bacteroidetes, Planctomycetes, Proteobacteria, Cyanobacteria, and Verrucomicrobia) and one class (Bacteroidia) increased on the skin of participants in the intervention group while no changes were observed in the placebo group. The number of nodes and edges in the co-occurrence networks of the skin bacteria increased on average three times more in the intervention group than in the placebo group. The plasma levels of the immunomodulatory cytokine interleukin 10 (IL-10) increased in the intervention group when compared with the placebo group. A similar trend was observed in the interleukin 17A (IL-17A) levels and in the IL-10:IL-17A ratios. Participants in both groups reported high satisfaction and adherence to the trial. The current study provides evidence in support of the core assumption of the hygiene and biodiversity hypotheses of immune-mediated diseases. Indoor urban gardening offers a meaningful and convenient approach for increasing year-round exposure to environmental microbiota, paving the way for other prophylactic practices that might help prevent immune-mediated diseases.

Soil intake modifies the gut microbiota and alleviates Th2-type immune response in an ovalbumin-induced asthma mouse model.

Background: A low-clean living environment (LCLE) can increase gut microbial diversity and prevent allergic diseases, whereas gut microbial dysbiosis is closely related to the pathogenesis of asthma. Our previous studies suggested that soil in the LCLE is a key factor in shaping intestinal microbiota. We aimed to explore whether sterilized soil intake as a prebiotic while being incubated with microbes in the air can attenuate mouse asthma inflammation by modifying gut microbiota. Methods: 16S rRNA gene sequencing was used to analyze the gut microbial composition, in combination with immune parameters measured in the lung and serum samples. Results: 16S rRNA gene sequencing results showed significant differences in the fecal microbiota composition between the test and control mice, with a higher abundance of Allobaculum, Alistipes, and Lachnospiraceae_UCG-001, which produce short-chain fatty acids and are beneficial for health in the test mice. Soil intake significantly downregulated the concentrations of IL-4 and IL-9 in serum and increased the expression of IFN-γ, which regulated the Th1/Th2 balance in the lung by polarizing the immune system toward Th1, alleviating ovalbumin-induced asthma inflammation. The effect of sensitization on gut microbiota was greater than that of air microbes and age together but weaker than that of soil. Conclusions: Soil intake effectively reduced the expression of inflammatory cytokines in asthmatic mice, possibly by promoting the growth of multiple beneficial bacteria. The results indicated that the development of soil-based prebiotic products might be used for allergic asthma management, and our study provides further evidence for the hygiene hypothesis.

Maternal-driven immune education in offspring.

Maternal environmental exposures, particularly during gestation and lactation, significantly influence the immunological development and long-term immunity of offspring. Mammalian immune systems develop through crucial inputs from the environment, beginning in utero and continuing after birth. These critical developmental windows are essential for proper immune system development and, once closed, may not be reopened. This review focuses on the mechanisms by which maternal exposures, particularly to pathogens, diet, and microbiota, impact offspring immunity. Mechanisms driving maternal-offspring immune crosstalk include transfer of maternal antibodies, changes in the maternal microbiome and microbiota-derived metabolites, and transfer of immune cells and cytokines via the placenta and breastfeeding. We further discuss the role of transient maternal infections, which are common during pregnancy, in providing tissue-specific immune education to offspring. We propose a "maternal-driven immune education" hypothesis, which suggests that offspring can use maternal encounters that occur during a critical developmental window to develop optimal immune fitness against infection and inflammation.

The gut-lung axis and asthma susceptibility in early life.

Asthma is the most common chronic disease among children, with more than 300 million cases worldwide. Over the past several decades, asthma incidence has grown, and epidemiological studies identify the modernized lifestyle as playing a strong contributing role in this phenomenon. In particular, lifestyle factors that modify the maternal gut microbiome during pregnancy, or the infant microbiome in early life, can act as developmental programming events which determine health or disease susceptibility later in life. Microbial colonization of the gut begins at birth, and factors such as delivery mode, breastfeeding, diet, antibiotic use, and exposure to environmental bacteria influence the development of the infant microbiome. Colonization of the gut microbiome is crucial for proper immune system development and disruptions to this process can predispose a child to asthma development. Here, we describe the importance of early-life events for shaping immune responses along the gut-lung axis and why they may provide a window of opportunity for asthma prevention.

Alternatives to antibiotics in pig production: looking through the lens of immunophysiology.

In the livestock production system, the evolution of porcine gut microecology is consistent with the idea of "The Hygiene Hypothesis" in humans. I.e., improved hygiene conditions, reduced exposure to environmental microorganisms in early life, and frequent use of antimicrobial drugs drive immune dysregulation. Meanwhile, the overuse of antibiotics as feed additives for infectious disease prevention and animal growth induces antimicrobial resistance genes in pathogens and spreads related environmental pollutants. It justifies our attempt to review alternatives to antibiotics that can support optimal growth and improve the immunophysiological state of pigs. In the current review, we first described porcine mucosal immunity, followed by discussions of gut microbiota dynamics during the critical weaning period and the impacts brought by antibiotics usage. Evidence of in-feed additives with immuno-modulatory properties highlighting probiotics, prebiotics, and phytobiotics and their cellular and molecular networking are summarized and reviewed. It may provide insights into the immune regulatory mechanisms of antibiotic alternatives and open new avenues for health management in pig production.

Update on the association between Helicobacter pylori infection and asthma in terms of microbiota and immunity.

H. pylori is a gram-negative bacterium that is usually acquired in childhood and can persistently colonize the gastric mucosa of humans, affecting approximately half of the world's population. In recent years, the prevalence of H. pylori infection has steadily reduced while the risk of allergic diseases has steadily climbed. As a result, epidemiological research indicates a strong negative association between the two. Moreover, numerous experimental studies have demonstrated that eradicating H. pylori increases the risk of allergic diseases. Hence, it is hypothesized that H. pylori infection may act as a safeguard against allergic diseases. The hygiene hypothesis, alterations in gut microbiota, the development of tolerogenic dendritic cells, and helper T cells could all be involved in H. pylori's ability to protect against asthma. Furthermore, Studies on mice models have indicated that H. pylori and its extracts are crucial in the management of asthma. We reviewed the in-depth studies on the most recent developments in the relationship between H. pylori infection and allergic diseases, and we discussed potential mechanisms of the infection's protective effect on asthma in terms of microbiota and immunity. We also investigated the prospect of the application of H. pylori and its related components in asthma, so as to provide a new perspective for the prevention or treatment of allergic diseases.

Evolutionary medicine approaches to chronic disease: The case of irritable bowel syndrome.

Irritable bowel syndrome (IBS), a gastrointestinal disease, is a global phenomenon correlated with industrialization. We propose that an evolutionary medicine approach is useful to understand this disease from an ultimate perspective and conducted a scoping literature review to synthesize the IBS literature within this framework. Our review suggests five potential evolutionary hypotheses for the cause of IBS, including (a) a dietary mismatch accompanying a nutritional transition, (b) an early hygienic life environment leading to the immune system and microbiotic changes, (c) an outcome of decreased physical activity, (d) a response to changes in environmental light-dark cycles, and (e) an artifact of an evolved fight or flight response. We find key limitations in the available data needed to understand early life, nutritional, and socioeconomic experiences that would allow us to understand evolutionarily relevant risk factors and identify a need for further empirical research to distinguish potential causes and test evolutionary hypotheses.

Update on the role of genetic factors, environmental factors and allergens in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation. OBJECTIVE: This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015. MATERIALS AND METHODS: Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.

Sterile soil mitigates the intergenerational loss of gut microbial diversity and anxiety-like behavior induced by antibiotics in mice.

The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.

The preprogrammed anti-inflammatory phenotypes of CD11chigh macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma.

BACKGROUND: Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined. METHODS: BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages. RESULTS: We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg. CONCLUSION: Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.

Atopic outcomes at 2 years in the CORAL cohort, born in COVID-19 lockdown.

INTRODUCTION: The CORAL study is a cohort of infants born during the first weeks of the first SARS-CoV-2 (COVID-19) lockdown. This cohort has had lower antibiotic exposure, higher breastfeeding rates and lower infection rates, especially in the first year of life. We hypothesized that the altered early-life environment of infants born during lockdown would change the incidence of allergic conditions. METHODS: This longitudinal, observational study followed 365 infants born between March and May 2020 from enrolment to the age of 2 years. Infants attended three research appointments at 6-, 12-, and 24-months and completed detailed questionnaires. At research appointments, children had skin prick testing, and atopic dermatitis (AD) assessment. Statistical analysis focused on changes within the group at different time points, the influence of specific environmental factors on allergic risk and compared the incidence of atopic conditions with a pre-pandemic Irish infant cohort, BASELINE. RESULTS: AD was more common in CORAL group at both 12 (26.5% vs. 15.5%; p < .001) and 24 months (21.3% vs. 15.9%; p = .02) compared with pre-pandemic BASELINE cohort. Within the CORAL group, those with AD at both 12- and 24-month appointments had a more severe AD phenotype associated with a higher risk of allergic sensitization. There was less milk (0% vs. 1%; p = .09), peanut (0.6% vs. 1.8%; p = .3), and egg allergy (0% vs. 2.9%; p < .001) in the CORAL group at 24 months compared with the BASELINE cohort. Aeroallergen sensitization increased between 12 and 24 months in the CORAL cohort (1.5% vs. 8.9%; p < .001), as did parent-reported wheezing episodes (9% vs. 24%; p < .001). CONCLUSIONS: Despite higher AD incidence in the CORAL cohort, the incidence of food sensitization and allergy are lower than expected pre-pandemic rates possibly reflecting the early introduction and maintenance of dietary allergens enhanced by changes in infant infections, antibiotic use, and breastfeeding in the first 2 years of life in the group. These beneficial effects of the lockdown could be outweighing the expected risk of less early-life microbial encounters outlined by the hygiene hypothesis.

Association between Helicobacter pylori Infection and Eosinophilic Esophagitis.

Background/Aims: This study examined the association between eosinophilic esophagitis (EoE) and Helicobacter pylori (H. pylori) infection. Methods: A single tertiary referral center case-control study was performed. EoE patients diagnosed at Seoul National University Bundang Hospital from July 2003 to March 2022 were reviewed retrospectively. Forty-five EoE patients were included in the analysis. For each EoE patient, two age and sex-matched normal controls were selected randomly from an outpatient population who received upper gastrointestinal endoscopy. Results: Although 17 out of 90 (18.9%) controls had a H. pylori infection, only two out of 45 (4.4%) EoE patients showed evidence of a H. pylori infection. EoE was inversely associated with a H. pylori infection (odds ratio 0.20, 95% confidence interval 0.04-0.91, p=0.044). Conclusions: An inverse association was observed between H. pylori infection and EoE. Further prospective studies will be needed to validate the protective effects of H. pylori infection for EoE.

Evaluating the influence of environmental risk factors on inflammatory bowel diseases: a case-control study.

Aim: This study aimed to examine the environmental factors associated in Iranian patients with inflammatory bowel disease (IBD). Background: The role of environmental factors in the development of IBD remains uncertain. Methods: In this case-control study, the patients with IBD referred to the Taleghani Hospital, Tehran, Iran, were recruited from 2017 to 2019. Controls were matched by sex. Data were collected using the designed questionnaire and also valid questionnaire such Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) for sleep quality and anxiety/depression, respectively. Conditional logistic regression models were used to estimate adjusted odds ratios (ORs). Results: The study population included 200 individuals: 100 (50%) IBD patients and 100 (50%) controls. Age under 50, marital status, sleep difficulties, vitamin D insufficiency, anxiety/depression, dietary fiber deficit, post-menopausal hormone treatment, oral contraceptives, and antibiotics were all prognostic factors for IBD on the univariate analysis (P< 0.005). In multivariate analysis, the risk of IBD was significantly increased with 50 years (OR: 6.699, 95%CI: 3.271-8.662, P=0.017), abnormal sleep status (OR: 6.383, 95%CI: 3.389-7.19, P=0.001), and using oral contraceptive (OR: 7.426, 95%CI: 5.327-9.865, P=0.001). However, the risk of IBD was significantly decreased with older age (OR: 0.795, 95%CI: 0.697-0.907, P=0.001) and married status (OR: 0.008, 95%CI: 0.001-0.438, P=0.018). Conclusion: Data suggest that the environmental factors play a significant role in the etiology of IBD and probably on the disease course. While the evidence for some factors is strong, many factors require further supportive data.

Subcutaneous Mycobacterium vaccae ameliorates the effects of early life adversity alone or in combination with chronic stress during adulthood in male and female mice.

Chronic psychosocial stress is a burden of modern society and poses a clear risk factor for a plethora of somatic and affective disorders, of which most are associated with an activated immune status and chronic low-grade inflammation. Preclinical and clinical studies further suggest that a failure in immunoregulation promotes an over-reaction of the inflammatory stress response and, thus, predisposes an individual to the development of stress-related disorders. Therefore, all genetic (i.e., sex) and environmental (i.e., early life adversity; ELA) factors facilitating an adult's inflammatory stress response are likely to increase their stress vulnerability. In the present study we investigated whether repeated subcutaneous (s.c.) administrations with a heat-killed preparation of Mycobacterium vaccae (M. vaccae; National Collection of Type Cultures (NCTC) 11659), an abundant soil saprophyte with immunoregulatory properties, are protective against negative behavioral, immunological and physiological consequences of ELA alone or of ELA followed by chronic psychosocial stress during adulthood (CAS) in male and female mice. ELA was induced by the maternal separation (MS) paradigm, CAS was induced by 19 days of chronic subordinate colony housing (CSC) in males and by a 7-week exposure to the social instability paradigm (SIP) in females. Our data indicate that ELA effects in both sexes, although relatively mild, were to a great extent prevented by subsequent s.c. M. vaccae administrations. Moreover, although the use of different paradigms for males and females impedes a direct comparison, male mice seemed to be more susceptible to CAS than females, with only females benefitting slightly from the stress protective effects of s.c. M. vaccae administrations when given prior to CAS alone. Finally, our data support the hypothesis that female mice are more vulnerable to the additive effects of ELA and CAS than male mice and that s.c. M. vaccae administrations subsequent to ELA but prior to CAS are protective in both sexes. Taken together and considering the limitation that CAS in males and females was induced by different paradigms, our findings are consistent with the hypotheses that murine stress vulnerability during different phases of life is strongly sex dependent and that developing immunoregulatory approaches, such as repeated s.c. administrations with immunoregulatory microorganisms, have potential for prevention/treatment of stress-related disorders.

Delayed acquisition of airway commensals in antibiotic naïve children and its relationship with wheezing in rural Ecuador.

Introduction: The hygiene hypothesis identified a relationship between living in rural areas and acquiring protective environmental factors against the development of asthma and atopy. In our previous study, we found a correlation between particular bacterial species and early-onset wheezing in infants from the rural tropics of Ecuador who were corticosteroid-naïve and had limited antibiotic exposure. We now describe a longitudinal study of infants conducted to determine the age-related changes of the microbiome and its relationship with wheezing. Methods: We performed an amplicon sequencing of the 16S rRNA bacterial gene from the oropharyngeal samples obtained from 110 infants who had a history of recurrent episodic wheezing sampled at different ages (7, 12, and 24 months) and compared it to the sequencing of the oropharyngeal samples from 150 healthy infants sampled at the same time points. Bioinformatic analyses were conducted using QIIME and R. Results: As expected, the microbiota diversity consistently increased as the infants grew older. Considering age-based microbiota changes, we found that infants with wheeze had significantly lower species richness than the healthy infants at 7 months, but not at 12 or 24 months. Most of the core and accessory organisms increased in abundance and prevalence with age, except for a few which decreased. At 7 months of age, infants with wheeze had notably higher levels of a single Streptococcus operational taxonomic unit and core microbiota member than controls. Conclusions: In a cohort with limited antibiotic and corticosteroid use, a progressively more complex and diverse respiratory microbial community develops with age. The respiratory microbiota in early life is altered in infants with wheeze, but this does not hold true in older infants.

Siblings and risk of allergic rhinitis: A systematic review and meta-analysis.

Following the "hygiene hypothesis" and the increase in the prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. The aim of this study was to synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self-reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment were performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta-analysis with robust variance estimation (RVE). Seventy-six reports with >2 million subjects were identified. Being second- or later-born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95% CI 0.73-0.86) and ever (RR 0.77, 95% CI 0.68-0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83-0.95) and allergic rhinoconjunctivitis (RR 0.92, 95% CI 0.86-0.98). These effects were unchanged across age, time period, and geographical regions. Our findings thus indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.