A population-based study on associations of stool microbiota with atopic diseases in school-age children.

BACKGROUND: Infants with less diverse gut microbiota seem to have higher risks of atopic diseases in early life, but any associations at school age are unclear. OBJECTIVES: This study sought to examine the associations of diversity, relative abundance, and functional pathways of stool microbiota with atopic diseases in school-age children. METHODS: We performed a cross-sectional study within an existing population-based prospective cohort among 1440 children 10 years of age. On stool samples, 16S ribosomal RNA gene sequencing was performed, and taxonomic and functional tables were produced. Physician-diagnosed eczema, allergy, and asthma were measured by questionnaires, allergic sensitization by skin prick tests, and lung function by spirometry. RESULTS: The α-diversity of stool microbiota was associated with a decreased risk of eczema (odds ratio [OR], 0.98; 95% CI, 0.97, 1.00), and ß-diversity was associated with physician-diagnosed inhalant allergy (R2 = 0.001; P = .047). Lachnospiraceae, Ruminococcaceae_UCG-005, and Christensenellaceae_R-7_group species were associated with decreased risks of eczema, inhalant allergic sensitization, and physician-diagnosed inhalant allergy (OR range, 0.88-0.94; 95% CI range, 0.79-0.96 to 0.88-0.98), while Agathobacter species were associated with an increased risk of physician-diagnosed inhalant allergy (OR, 1.23; 95% CI, 1.08-1.42). Functional pathways related to heme and terpenoid biosynthesis were associated with decreased risks of physician-diagnosed inhalant allergy and asthma (OR range, 0.89-0.86; 95% CI range, 0.80-0.99 to 0.73-1.02). No associations of stool microbiota with lung function were observed. CONCLUSIONS: The diversity, relative abundance and functional pathways of stool microbiota were most consistently associated with physician-diagnosed inhalant allergy in school-age children and less consistently with other atopic diseases.

Differences in microbiota between acute and chronic perianal eczema.

ABSTRACT: Microbiota has been suggested to play a role in patients with intestinal and cutaneous diseases. However, the profiling of perianal eczema microbiota has not been described. We have explored the general profile and possible differences between acute and chronic perianal eczema. A total of 101 acute perianal eczema (APE) and 156 chronic perianal eczema (CPE) patients were enrolled in this study and the perianal microbiota was profiled via Illumina sequencing of the 16S rRNA V4 region.The microbial α-diversity and structure are similar in APE and CPE patients; however, the perianal microbiota of the APE patients had a higher content of Staphylococcus (22.2%, P < .01) than that of CPE patients. Top10 genera accounting for more than 60% (68.81% for APE and 65.47% for CPE) of the whole microbiota, including Prevotella, Streptococcus, and Bifidobacterium, show an upregulation trend in the case of APE without reaching statistically significant differences. This study compared the microbiota profiles of acute and chronic perianal eczema. Our results suggest that the microbiota of acute perianal eczema patients is enriched in Staphylococcus compared with that in the chronic group. Our findings provide data for further studies.

Association of early-life gut microbiome and lifestyle factors in the development of eczema in Hong Kong infants.

Childhood eczema is common but its prevalence is variable in different regions of the world. In this study, we explore the associations of various risk factors such as the microbiome, environment, lifestyle, diet and maternal stress with the development of eczema among infants in Hong Kong. Upon enrolment in the study, the infants' parents provided demographic data by self-reporting. At enrolment and 1 year after birth, the infants' allergic conditions, lifestyles and dietary factors and the degree of maternal stress were assessed using various questionnaires. The infants' gut microbiomes were analysed by 16S RNA sequencing, and the longitudinal changes in various bacterial strains were compared between control and eczema-affected groups. Multivariate analyses (after adjustment for other significant factors) revealed that the changes in the abundance of Hungatella hathewayi in the gut were significantly associated with the development of eczema (p = 0.005). In conclusion, the increased abundance of Hungatella hathewayi was associated with an increased risk of developing eczema by 1 year of age. This study thus explored the potential risk factors for the development of eczema in Hong Kong infants, and sheds light on the possible association between early-life gut microbiome and other environmental factors.

Altered Gut Microbiome and Environmental Factors Associated with Development of Eczema in Hong Kong Infants: A 4-Month Pilot Study.

Eczema is a multifactorial skin disease that affects 20% of children worldwide and has a complex relationship with microbial, nutritional, parental and environmental factors. In this study, we investigated the potential association of eczema with the gut microbiome and environmental factors. One hundred and fifty-two newborn subjects and their mothers were recruited within 10 days postnatally at the Prince of Wales Hospital in Hong Kong, China and asked to complete questionnaires on allergies, maternal diet and environmental assessment at enrolment. Then, the participants were classified as with or without eczema at four months after birth based on the Comprehensive Early Childhood Allergy Questionnaire (CECAQ) and SCORing Atopic Dermatitis (SCORAD) index (n = 48, with 24 in each group). Stool samples were collected from both groups at the same time. Microbial DNA was extracted from each stool sample, and 16S rRNA sequencing was performed to analyze the gut microbiome profiles of the subjects. Our results indicated that the abundance of Bifidobacterium was significantly higher in the eczema group than in the control group (p = 0.04). A multivariable logistic regression analysis was conducted, and the results showed that the father's education level and maternal intake of cereal products and nutritional supplements during pregnancy were associated with the development of eczema (p = 0.008, 0.032 and 0.015, respectively). In conclusion, this study provided preliminary information about the potential risk factors of eczema development in Hong Kong infants in support of a future full study.

Effects of gut microbiome and environment on the development of eczema in Chinese infants.

BACKGROUND: Eczema is a relapsing and persistent inflammatory skin disease affecting about one-fifth of children worldwide. As in other developed countries, the prevalence of this chronic disease in Hong Kong is approximately 30%. Moreover, the number of local cases reported has been on a rising trend since 1995. Eczema frequently starts in early infancy. A total of 45% of all cases begin within the first six months of life, 60% during the first year and 85% before the age of 5. The pathophysiology of eczema is multi-factorial and is a complex inter-relationship between skin barrier, genetic predisposition, immunologic development, microbiome, environment, nutrition, and pharmacological and psychological factors. OBJECTIVE: To characterize the longitudinal changes of gut microbial profile in early childhood and to examine the association between gut microbiome diversity, environmental factors and the development of eczema in early childhood. METHOD: We will conduct a longitudinal cohort study that follows 1250 Hong Kong Chinese infants for 2 years and assess the gut microbiome and other potential environmental factors in the aetiology of eczema. Parents will be asked to provide demographic data, their infant birth data, allergy condition, diet, environmental conditions as well as the data on maternal stress. Stool specimen will be collected for gut microbiome diversity analysis. We will examine newborn infants at enrollment, at 4 months, 1 year and 2 years after birth. EXPECTED RESULTS: This study will evaluate the association between gut microbiome, environmental factors and the development of eczema in Chinese infants. Findings from this study may be used to develop a predictive path model to guide effective health promotion, disease prevention and management.

Interventions to reduce Staphylococcus aureus in the management of eczema.

BACKGROUND: Staphylococcus aureus (S. aureus) can cause secondary infection in eczema, and may promote inflammation in eczema that does not look infected. There is no standard intervention to reduce S. aureus burden in eczema. It is unclear whether antimicrobial treatments help eczema or promote bacterial resistance. This is an update of a 2008 Cochrane Review. OBJECTIVES: To assess the effects of interventions to reduce S. aureus for treating eczema. SEARCH METHODS: We updated our searches of the following databases to October 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched five trials registers and three sets of conference proceedings. We checked references of trials and reviews for further relevant studies. We contacted pharmaceutical companies regarding ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials of products intended to reduce S. aureus on the skin in people diagnosed with atopic eczema by a medical practitioner. Eligible comparators were a similar treatment regimen without the anti-staphylococcal agent. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were participant- or assessor-rated global improvement in symptoms/signs, quality of life (QOL), severe adverse events requiring withdrawal, minor adverse events, and emergence of antibiotic-resistant micro-organisms. MAIN RESULTS: We included 41 studies (1753 analysed participants) covering 10 treatment categories. Studies were conducted mainly in secondary care in Western Europe; North America; the Far East; and elsewhere. Twelve studies recruited children; four, adults; 19, both; and six, unclear. Fifty-nine per cent of the studies reported the mean age of participants (range: 1.1 to 34.6 years). Eczema severity ranged from mild to severe. Many studies did not report our primary outcomes. Treatment durations ranged from 10 minutes to 3 months; total study durations ranged from 15 weeks to 27 months. We considered 33 studies at high risk of bias in at least one domain. We present results for three key comparisons. All time point measurements were taken from baseline. We classed outcomes as short-term when treatment duration was less than four weeks, and long-term when treatment was given for more than four weeks. Fourteen studies evaluated topical steroid/antibiotic combinations compared to topical steroids alone (infective status: infected (two studies), not infected (four studies), unspecified (eight studies)). Topical steroid/antibiotic combinations may lead to slightly greater global improvement in good or excellent signs/symptoms than topical steroid alone at 6 to 28 days follow-up (risk ratio (RR) 1.10, 95% confidence interval (CI) 1.00 to 1.21; 224 participants; 3 studies, low-quality evidence). There is probably little or no difference between groups for QOL in children, at 14 days follow-up (mean difference (MD) -0.18, 95% CI -0.40 to 0.04; 42 participants; 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: severe adverse events were rare (follow-up: between 6 to 28 days): both groups reported flare of dermatitis, worsening of the condition, and folliculitis (325 participants; 4 studies). There were fewer minor adverse events (e.g. flare, stinging, itch, folliculitis) in the combination group at 14 days follow-up (218 participants; 2 studies). One study reported antibiotic resistance in children at three months follow-up, with similar results between the groups (65 participants; 1 study). Four studies evaluated oral antibiotics compared to placebo (infective status: infected eczema (two studies), uninfected (one study), one study's participants had colonisation but no clinical infection). Oral antibiotics may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo (RR 0.80; 95% CI 0.18 to 3.50; 75 participants; 2 studies, low-quality evidence). There is probably little or no difference between groups for QOL (in infants and children) at 14 days follow-up (MD 0.11, 95% CI -0.10 to 0.32, 45 participants, 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: adverse events requiring treatment withdrawal between 14 to 28 days follow-up were very rare, but included eczema worsening (both groups), loose stools (antibiotic group), and Henoch-Schönlein purpura (placebo group) (4 studies, 199 participants). Minor adverse events, including nausea, vomiting, diarrhoea, and stomach and joint pains, at 28 days follow-up were also rare and generally low in both groups (1 study, 68 infants and children). Antibiotic resistance at 14 days was reported as similar in both groups (2 studies, 98 infants and children). Of five studies evaluating bleach baths compared to placebo (water) or bath emollient (infective status: uninfected (two studies), unspecified (three studies)), one reported global improvement and showed that bleach baths may make no difference when compared with placebo at one month follow-up (RR 0.78, 95% CI 0.37 to 1.63; 36 participants; low-quality evidence). One study showed there is probably little or no difference in QOL at 28 days follow-up when comparing bleach baths to placebo (MD 0.90, 95% CI -1.32 to 3.12) (80 infants and children; moderate-quality evidence). We are uncertain if the groups differ in the likelihood of treatment withdrawals due to adverse events at two months follow-up (only one dropout reported due to worsening itch (placebo group)) as the quality of evidence was very low (1 study, 42 participants). One study reported that five participants in each group experienced burning/stinging or dry skin at two months follow-up, so there may be no difference in minor adverse events between groups (RR 1.00, 95% CI 0.35 to 2.87, 36 participants, low-quality evidence). Very low-quality evidence means we are also uncertain if antibiotic resistance at four weeks follow-up is different between groups (1 study, 80 participants ≤ 18 years). AUTHORS' CONCLUSIONS: We found insufficient evidence on the effects of anti-staphylococcal treatments for treating people with infected or uninfected eczema. Low-quality evidence, due to risk of bias, imprecise effect estimates and heterogeneity, made pooling of results difficult. Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required.

THE STUDY OF SKIN AUTOFLORA'S PATHOGENIC PROPERTIES IN PATIENTS DIAGNOSED WITH ATOPIC DERMATITIS.

The development of atopic dermatitis (AD) is often associated with the presence of pathogenic microflora in the skin's biotope against the background of acute immunological disorders of the microorganism. In this case, the leading role is played by Staphylococcus aureus, which is seeded in 80-95% of patients diagnosed with AD. The clinical significance of the pathogen is determined by its ability to actively survive in the biotope, aided by a wide range of pathogenicity factors of this microorganism. Goal of research - to study the activity levels of pathogenicity factors and the persistence of staphylococci clinical autostrains isolated from different topodems of the skin of patients diagnosed with AD. The object of study was 101 laboratory strain of the skin's staphylococci of 50 patients diagnosed with AD and 39 control strains isolated from 20 generally healthy individuals. Isolation of microorganisms and bacteriological studies of their pathogenic characteristics were carried out using the methods of classical bacteriology. It was revealed that the qualitative and quantitative characteristics of the antilysocyme activity (ALA), the anti-interferon activity (AIA) and the adhesive properties of the strains isolated from the affected skin areas were significantly higher than that of the cultures isolated from the intact areas. The data obtained indicate the ability of these pathogens to adversely affect the course of the pathological process in the skin.

The Human Microbiota and Its Relationship with Allergies.

Allergic diseases have been increasing to epidemic proportions during the past century, especially in high-income countries. Recent evidence suggests there might be a link between the allergy epidemic and reduced microbial exposures, resulting from a rapidly evolved modern lifestyle, including changed diets, health and hygiene standards, and daily habits. Recently it has become clear that the microbial communities in our respiratory system and our gut, as well as on our skin, may play a key role in shaping our physiology, and influencing our health. We are only beginning to understand the mechanisms by which the human microbiota may be regulating the immune system, and sudden changes in the composition of the microbiota may have profound effects, linked with an increased risk of developing chronic inflammatory disorders, including allergies.

Staphylococcus aureus colonization and chronic hand eczema: a multicenter clinical trial.

Chronic hand eczema is a common chronic inflammatory skin disease that influences public health. Staphylococcus aureus colonization plays important roles in chronic hand eczema morbidity and progression, which also correlated to chronicity and severity of the disease. In this multicenter clinical trial, we aim to investigate the relationship between S. aureus colonization and chronic hand eczema. Eighty patient volunteers diagnosed with chronic hand eczema in 4 hospitals from 4 cities participated in this study. Staphylococcus aureus colonization was determined using Polymerase Chain Reaction and fluorescent labeling probe to rapidly detect the endemic thermostable nuclease gene nuc of S. aureus in clinical samples. All patients were treated with Halometasone Triclosan Cream for 2 weeks. The changes of clinical symptom scores were observed during the follow-up time. We found that the severity of chronic hand eczema was related to S. aureus colonization. Chronic hand eczema would remain severer than others if S. aureus colonization was not eliminated. Eliminating S. aureus colonization could provide good effectiveness in treatment of chronic hand eczema. Therefore, we make a proposal that detection and treatment of S. aureus should be considered in the clinical treatment of chronic hand eczema.

Variations in early gut microbiome are associated with childhood eczema.

We assessed the relationship between gut microbiome profile and childhood eczema in 172 subjects (age < 3 years, healthy group N = 123, eczema group N = 49) utilizing 16S rRNA gene sequencing. Lower relative abundance of Bifidobacterium was shown to be associated with childhood eczema. Considering that developmental and environmental factors could modify the state of children's gut microbiome, we divided the samples into four age groups: 0-0.5 years, 0.5-1 years, 1-2 years and 2-3 years for farther analyses. Data revealed significant inter-group differences between healthy and eczema samples in all age groups, and decreased microbial diversity was most significantly found in children with eczema of age 2-3 years old. Decreased abundance of Bifidobacterium was a major finding in eczema groups from 0.5-3 years compared to the age matched healthy controls, but not significant in children younger than 6 month old. Of note, Bifidobacterium operational taxonomic units were identified by Random Forest with highly predictive power of 0.83 (AUC = 0.83) in ROC analysis, which also confirmed its role as a key genus that is associated with eczema. To verify the sequencing results, we performed quantitative polymerase chain reaction of Bifidobacterium and Bacteroides in the same cohort, and in a new eczema cohort (N = 57) for validation. Significantly, lower Bifidobacterium quantities were found in both eczema groups with an age range of 0.5-3 years. These results suggest variations in early gut microbiome are associated with childhood eczema.

Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age.

Background: Neonatal antibiotics disturb the developing gut microbiome and are therefore thought to influence the developing immune system, but exact mechanisms and health consequences in later life still need to be elucidated. Therefore, we investigated whether neonatal antibiotics influence inflammatory markers at 1 year of age. In addition, we determined whether health problems during the first year of life, e.g., allergic disorders (eczema and wheezing) or infantile colics, were associated with changes in the circulating immune marker profile at 1 year of age. Methods: In a subgroup (N = 149) of the INCA-study, a prospective birth-cohort study, a blood sample was drawn from term born infants at 1 year of age and analyzed for 84 immune related markers using Luminex. Associations of antibiotic treatment, eczema, wheezing, and infantile colics with immune marker concentrations were investigated using a linear regression model. The trial is registered as NCT02536560. Results: The use of broad-spectrum antibiotics in the first week of life, was significantly associated with different levels of inflammatory markers including sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70 at 1 year of age. Eczema was associated with decreased concentrations of IFNα, IFNγ, TSLP, CXCL9, and CXCL13, but increased concentrations of CCL18 and Galectin-3. Wheezing, independent of antibiotic treatment, was positively associated to TNF-R2 and resistin. Infantile colics were positively associated to IL-31, LIGHT, YKL-40, CXCL13, sPD1, IL1RI, sIL-7Ra, Gal-1, Gal-9, and S100A8 at 1 year of age, independent of early life antibiotic treatment. Conclusion: In this explorative study, we identified that neonatal antibiotics are associated with immunological alterations at 1 year of age and that, independent of the antibiotic treatment, infantile colics were associated with alterations within gut associated markers. These findings support the importance of the first host microbe interaction in early life immune development.

Detection and treatment of Staphylococcus aureus colonization in chronic hand eczema: a multicenter study.

Background: Chronic hand eczema (CHE) is a common chronic inflammatory skin disease of the hands that influences public health. Staphylococcus aureus (SA) colonization plays an important role in CHE morbidity and progression, which also correlated to chronicity and severity of the disease. Materials and methods: From October 1 to November 31, 80 patient volunteers with CHE and 10 healthy volunteers were chosen from the four cities. Polymerase chain reaction (PCR) as a new diagnostic method for SA and methicillin-resistant Staphylococcus aureus (MRSA), was superior to the traditional method of germiculture. Results: We found that the colonization of SA was common in CHE in the multicenter study and topical antibiotic therapeutic was effective to SA colonization, whereas not to MRSA colonization. Conclusions: Our study revealed the present situation of SA colonization in four cities of China using a new method and had reference significance in anti-SA using a topical antibiotic.

Human Skin Microbiota in Various Phases of Atopic Dermatitis.

Skin microbiota can be used to assess the macroorganism's overall health. The quantitative and qualitative microbiota composition depends on the macroorganism's state, while microbiota bacteria can cause and maintain cutaneous inflammation, in turn worsening the macroorganism's state. This leads to placing additional focus on determination of skin microbiota when studying the pathogenesis of allergic dermatoses. We present the results of our study on the microbiota of apparently healthy skin in children with atopic eczema (AE) exacerbation and skin microbiota in remission. The study revealed that the skin microbiota in children with AE significantly differs from that of healthy controls. The differences include not the quantitative but also qualitative skin microbiota composition both on AE lesions and apparently healthy skin, where the bacterial number exceeds that on the skin of the control group children by 2-4 times. We also observed qualitative bacterial imbalance and appearance and prevalence of microorganisms not typical for healthy skin, where saprophytic Staphylococcus is the basis of microbiota, while Staphylococcus aureus was the basis in patients with AE. The skin microbiota in children with AE in remission also differed significantly from the skin microbial flora in healthy children. The skin in remission was highly contaminated with microorganisms, in particular pathogens, which indicates sustained alterations of skin microbiota as an unfavorable prognostic factor that can provoke disease relapse.

Lactobacillus rhamnosus GG in the Primary Prevention of Eczema in Children: A Systematic Review and Meta-Analysis.

Current guidelines recommend the use of probiotics to reduce the risk of eczema. It remains unclear which strain(s) to use. We systematically evaluated data on the efficacy of Lactobacillus rhamnosus GG (LGG) supplementation prenatally and/or postnatally for the primary prevention of eczema. The Cochrane Library, MEDLINE, and EMBASE databases were searched up to August 2018, with no language restrictions, for systematic reviews of randomized controlled trials (RCTs) and RCTs published afterwards. The primary outcome was eczema. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. Heterogeneity was explored using the I² statistics. The GRADE criteria were used to assess the overall quality of evidence supporting the primary outcome. Seven publications reporting 5 RCTs (889 participants) were included. High to moderate certainty in the body of evidence suggests that LGG supplementation (regardless of the timing of administration) did not reduce the risk of eczema. There was also no consistent effect on other allergic outcomes. This meta-analysis shows that LGG was ineffective in reducing eczema. It does not support the general recommendation to use probiotics for preventing eczema, unless specific strains would be indicated.

Staphylococcus aureus colonisation and its relationship with skin and soft tissue infection in New Zealand children.

New Zealand children suffer from high rates of skin and soft tissue infection (SSTI). Staphylococcus aureus colonisation is known to increase the risk of nosocomial infection. We aimed to determine whether S. aureus colonisation also increased the risk of community-onset SSTI. This study, performed within the Growing Up in New Zealand cohort, used interview and administrative data, and bacterial culture results from the nose, throat, and skin swabs collected at 4½ years of age. Multivariable log-binomial regression was used to derive adjusted risk ratios. S. aureus was isolated from 2225/5126 (43.4%) children. SSTI affected 1509/5126 (29.4%) children before age five. S. aureus colonisation at any site was associated with SSTI (aRR = 1.09, 95%CI 1.01-1.19), particularly in the year prior to swab collection (aRR = 1.18, 95%CI 1.02-1.37). The strongest association was between skin colonisation and SSTI within the year prior to swab collection (aRR = 1.47, 95%CI 1.14-1.84). Socioeconomic and ethnic variables remained independent determinants of SSTI. S. aureus colonisation was associated with an increased risk of community-onset SSTI. Socioeconomic and ethnic factors and eczema had independent effects on SSTI risk. Interventions which reduce the prevalence of S. aureus colonisation may be expected to reduce the incidence of community-onset SSTI.