Imbalance of Gut Streptococcus, Clostridium, and Akkermansia Determines the Natural Course of Atopic Dermatitis in Infant

PURPOSE: The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood.METHODS: Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry.RESULTS: Low levels of Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in transient AD infants compared with healthy and persistent AD infants.CONCLUSIONS: Compositions, functions and metabolites of the early gut microbiome are related to natural courses of AD in infants.

Leukocyte Telomere Length Reflects Prenatal Stress Exposure, But Does Not Predict Atopic Dermatitis Development at 1 Year

PURPOSE: Prenatal maternal stress affects offspring's atopic dermatitis (AD) development, which is thought to be mediated by the oxidative stress. We aimed to evaluate the difference in leukocyte telomere length (LTL), a marker for exposure to oxidative stress, according to the prenatal stress exposure and the later AD development. METHODS: From a birth cohort (the COhort for Childhood Origin of Asthma and allergic diseases) that had displayed a good epidemiologic association between the exposure to prenatal stress and AD development in the offspring, we selected 68 pairs of samples from 4 subject groups based on the level of prenatal maternal stress and later AD development. The LTL was measured from both cord blood and 1-year peripheral blood, and their LTLs were compared between subject groups. Finally, the proportion of AD development was examined in the subject groups that are reclassified based on subjects' exposure to prenatal stress and there LTL. RESULTS: Cord-blood LTL was shorter in prenatally stressed infants than in unstressed ones (P = 0.026), which difference was still significant when subjects became 1 year old (P = 0.008). LTL of cord blood, as well as one of the 1-year peripheral blood, was not different according to later AD development at 1 year (P = 0.915 and 0.174, respectively). Shorter LTL made no increase in the proportion of later AD development in either prenatally high-stressed or low-stressed groups (P = 1.000 and 0.473, respectively). CONCLUSIONS: Cord-blood LTL may reflect subjects' exposure to maternal prenatal stress. However, the LTL shortening is not a risk factor of increasing AD development until the age of 1, and a longer investigation may be necessary for validation. Currently, the results doubt the role of LTL shortening as a marker for risk assessment tool for the prenatal stress associated with AD development in the offspring.

The risk of preschool asthma at 2–4 years is not associated with leukocyte telomere length at birth or at 1 year of age

BACKGROUND: Exposure to prenatal stress is associated with offspring allergic-disease development, and oxidative stress may mediate this relationship. OBJECTIVE: We aimed to evaluate whether leukocyte telomere length (LTL) shortening, a marker for exposure to oxidative stress, in early life is associated with increased risk of asthma development during the preschool period. METHODS: We assessed the follow-up clinical data of a subgroup from a birth cohort whose LTLs had been measured from cord-blood and 1-year peripheral-blood samples. We examined whether the LTLs would be associated with asthma development at the age of 2–4 years. RESULTS: The data of 84 subjects were analyzed. LTLs were measured from the cord-blood and 1-year peripheral blood of 75 and 79 subjects, respectively. Among them, 14 subjects (16.7%) developed bronchial asthma between 2–4 years old. Prenatally stressed subjects had marginally increased odds of developing asthma (p = 0.097). There was no significant difference in the odds of preschool-asthma development between the groups with shorter and longer cord-blood LTLs (odds ratio [OR], 0.651; 95% confidence interval [CI], 0.184–2.306) or in the odds between the groups with shorter and longer 1-year peripheral-blood LTLs (OR, 0.448; 95% CI, 0.135–1.483). Finally, subjects with both higher prenatal stress and shorter LTLs did not have significantly higher odds of preschool-asthma development (for cord-blood: OR, 1.242; 95% CI, 0.353–4.368; for 1-year peripheral-blood: OR, 1.451; 95% CI, 0.428–4.919). CONCLUSION: There was no significant association between early life LTLs and higher risk of bronchial-asthma development during the preschool years.

Microbiome in the Gut-Skin Axis in Atopic Dermatitis

The microbiome is vital for immune system development and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the skin and the gut have recently been linked to alterations in immune responses and to the development of skin diseases, such as atopic dermatitis (AD). In this review, we summarize the recent findings on the gut and skin microbiome, highlighting the roles of major commensals in modulating skin and systemic immunity in AD. Although our understanding of the gut-skin axis is only beginning, emerging evidence indicates that the gut and skin microbiome could be manipulated to treat AD.

The role of rpoS, hmp, and ssrAB in Salmonella enterica Gallinarum and evaluation of a triple-deletion mutant as a live vaccine candidate in Lohmann layer chickens

Salmonella enterica Gallinarum (SG) causes fowl typhoid (FT), a septicemic disease in avian species. We constructed deletion mutants lacking the stress sigma factor RpoS, the nitric oxide (NO)-detoxifying flavohemoglobin Hmp, and the SsrA/SsrB regulator to confirm the functions of these factors in SG. All gene products were fully functional in wild-type (WT) SG whereas mutants harboring single mutations or a combination of rpoS, hmp, and ssrAB mutations showed hypersusceptibility to H2O2, loss of NO metabolism, and absence of Salmonella pathogenicity island (SPI)-2 expression, respectively. A triple-deletion mutant, SGDelta3 (SGDeltarpoSDeltahmpDeltassrAB), was evaluated for attenuated virulence and protection efficacy in two-week-old Lohmann layer chickens. The SGDelta3 mutant did not cause any mortality after inoculation with either 1 x 10(6) or 1 x 10(8) colony-forming units (CFUs) of bacteria. Significantly lower numbers of salmonellae were recovered from the liver and spleen of chickens inoculated with the SGDelta3 mutant compared to chickens inoculated with WT SG. Vaccination with the SGDelta3 mutant conferred complete protection against challenge with virulent SG on the chickens comparable to the group vaccinated with a conventional vaccine strain, SG9R. Overall, these results indicate that SGDelta3 could be a promising candidate for a live Salmonella vaccine against FT.

Characterization of an Extracytoplasmic Chaperone Spy in Protecting Salmonella against Reactive Oxygen/Nitrogen Species

Antimicrobial actions of reactive oxygen/nitrogen species (ROS/RNS) derived from products of NADPH oxidase and inducible nitric oxide (NO) synthase in host phagocytes inactivate various bacterial macromolecules. To cope with these cytotoxic radicals, pathogenic bacteria have evolved to conserve systems necessary for detoxifying ROS/RNS and repairing damages caused by their actions. In response to these stresses, bacteria also induce expression of molecular chaperones to aid in ameliorating protein misfolding. In this study, we explored the function of a newly identified chaperone Spy, that is localized exclusively in the periplasm when bacteria exposed to conditions causing spheroplast formation, in the resistance of Salmonella Typhimurium to ROS/RNS. A spy deletion mutant was constructed in S. Typhimurium by a PCR-mediated method of one-step gene inactivation with lambda Red recombinase, and subjected to ROS/RNS stresses. The spy mutant Salmonella showed a modest decrease in growth rate in NO-producing cultures, and no detectable difference of growth rate in H2O2 containing cultures, compared with that of wild type Salmonella. Quantitative RT-PCR analysis showed that spy mRNA levels were similar regardless of both stresses, but were increased considerably in Salmonella mutants lacking the flavohemoglobin Hmp, which are incapable of NO detoxification, and lacking an alternative sigma factor RpoS, conferring hypersusceptibility to H2O2. Results demonstrate that Spy expression can be induced under extreme conditions of both stresses, and suggest that the protein may have supportive roles in maintaining proteostasis in the periplasm where various chaperones may act in concert with Spy, thereby protecting bacteria against toxicities of ROS/RNS.

Prevalence of Hepatitis C Virus Infections and Distribution of Hepatitis C Virus Genotypes among Korean Blood Donors

BACKGROUND: Hepatitis C virus (HCV) remains a worldwide health-care burden. Prevalence rates vary and the distribution of genotypes depends on geographical location. Here, the recent prevalence of HCV infections and distribution of HCV genotypes among Korean blood donors were studied. METHODS: Between February 2005 and December 2009, a total of 11,064,532 donors were screened for anti-HCV and 11,412,690 donors were screened for HCV RNA. HCV genotyping was conducted for 748 blood donors with HCV RNA by using the line probe assay (VERSANT HCV Genotype 2.0 Assay, Bayer Healthcare, USA) after amplification of the 5'-untranslated and core regions of the genome. RESULTS: The anti-HCV prevalence was 0.16% (17,250/11,064,532). HCV RNA was detected in 959 out of the 11,412,690 donors (8.4/100,000). HCV RNA was more prevalent among women, donors who resided at harbor sites, and first-time donors. In addition, the prevalence of HCV RNA increased with age. The genotypes of 740 out of the 748 tested donors (98.9%) were identified. HCV genotype 1b (47.7%) and 2a/2c (35.0%) were dominant. Genotypes 2 (7.6%), 2b (2.3%), 3a (1.6%), 1a (1.3%), 1 (0.9%), 2v (0.5%), 1v (0.1%), and 3 (0.1%) were also identified. Genotype 4a/4c/4d (0.1%) was detected for the first time in one Korean blood donor. CONCLUSIONS: The distribution of HCV genotypes in Korea has not changed remarkably, with the exception of genotype 4a/4c/4d. A periodic study to monitor the prevalence of HCV infections and the distribution of HCV genotypes is required to identify emerging genotypes in Korea.

Analysis of the Effectiveness of Blotting Assays for Donor Blood Screening / 대한수혈학회지

BACKGROUND: Immunoblot assays (IBAs) have been widely used to confirm the reactivity of immunoassay. However, indeterminate (ID) results have shown the limits for interpreting IBAs. There is some debate about the benefit of these assays. We assessed the actual status of the IBAs for the donor screening process and we proposed more available algorithms. METHODS: We analyzed the data from the blood information management system of the Korean Red Cross. This study was approved by the Institutional Review Board of the KRC. The analyzed data included the present condition of various utilities and the results of the IBAs in the world. RESULTS: The infectivity of the ID results in IBAs seemed not to be high, but the safety could not be assured. IBA for HTLV was used as a confirmatory test in many countries. Most of the eligible blood donors could be saved by IBAs. CONCLUSION: IBAs seem to be valuable methods as supplemental and follow up tests for ID results. Furthermore, IBAs were useful to distinguish eligible blood donors. When donors show positive results on an immunoassay and NAT (HIV and HCV) concurrently, then IBA does not seem to be required. Only a RIBA for HCV is recommended for the donors showing a S/CO ratio above 2.0 on immunoassay. The additional alternative immunoassay would be effective in the HTLV screening algorithm.

The Frequency and Distribution of the ABO Subgroups in Korean Blood Donors / 대한수혈학회지

BACKGROUND: ABO subgroups are obstacles in blood typing and cross matching in the process of pre-transfusion. Correct ABO typing is important for ensuring safety of a transfusion. The ABO subgroups contain a lesser amount of antigen on red cells and this is a common cause of discrepancy between the results of cell and serum tests. This study was performed to analyze the frequency and distribution of the ABO subgroups in Korean blood donors. METHODS: ABO blood grouping was performed by an automated analyzer (PK7200/7300, Olympus, Japan) for the 3,397,983 donors from January 2007 to December 2009. The 1,868 donor samples that were suspected to have ABO subgroups were tested with adsorption/elution techniques. The results of the tests were analyzed and we received approval of the Institutional Review Board of the Korean Red Cross to publish this study. RESULTS: 1,771 donors out of the 1,868 donors who underwent the tests were finally identified as having ABO subgroups. The kinds of identified ABO subgroups were as follows; 118 donors with the A subgroup (A2, A3, Ax, Am, Ael), 237 donors with the B subgroup (B3, Bx, Bm, Bel) and 1,416 donors with the AB subgroup (A2B, A2B3, A1B3, AmB, A1Bm, A1Bel, AxB, A1Bx). The most frequently observed subgroups were A2B (496/1,868, 26.55%) and then A2B3 (457/1,868, 24.46%). The subgroups of 97 donors (5.19%) were not identified. CONCLUSION: This study was meaningful to provide data on the frequency and distribution of the ABO subgroups of Korean blood donors. A more sensitive technique such as genotyping could be useful to resolve cases with an unidentified subgroup.