Systematic review of the association between short chain fatty acids and allergic diseases.

We performed a systematic review to investigate the current evidence on the association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced and suggested as one mechanism on how gut microbiome affects the risk of allergic diseases. Medline, Embase and Web of Science were searched from data inception until September 2022. We identified 37 papers, of which 17 investigated prenatal or early childhood SCFAs and the development of allergic diseases in childhood, and 20 assessed SCFAs in patients with pre-existing allergic diseases. Study design, study populations, outcome definition, analysis method and reporting of the results varied between papers. Overall, there was some evidence showing that the three main SCFAs (acetate, propionate and butyrate) in the first few years of life had a protective effect against allergic diseases, especially for atopic dermatitis, wheeze or asthma and IgE-mediated food allergy in childhood. The association between each SCFA and allergic disease appeared to be different by disease and the age of assessment. Further research that can determine the potentially timing specific effect of each SCFA will be useful to investigate how SCFAs can be used in treatment or in prevention against allergic diseases.

Electrical impedance spectroscopy detects skin barrier dysfunction in childhood atopic dermatitis.

BACKGROUND: Skin barrier dysfunction is associated with the development of atopic dermatitis (AD), however methods to assess skin barrier function are limited. We investigated the use of electrical impedance spectroscopy (EIS) to detect skin barrier dysfunction in children with AD of the CARE (Childhood AlleRgy, nutrition, and Environment) cohort. METHODS: EIS measurements taken at multiple time points from 4 months to 3-year-old children, who developed AD (n = 66) and those who did not (n = 49) were investigated. Using only the EIS measurement and the AD status, we developed a machine learning algorithm that produces a score (EIS/AD score) which reflects the probability that a given measurement is from a child with active AD. We investigated the diagnostic ability of this score and its association with clinical characteristics and age. RESULTS: Based on the EIS/AD score, the EIS algorithm was able to clearly discriminate between healthy skin and clinically unaffected skin of children with active AD (area under the curve 0.92, 95% CI 0.85-0.99). It was also able to detect a difference between healthy skin and AD skin when the child did not have active AD. There was no clear association between the EIS/AD score and the severity of AD or sensitisation to the tested allergens. The performance of the algorithm was not affected by age. CONCLUSIONS: This study shows that EIS can detect skin barrier dysfunction and differentiate skin of children with AD from healthy skin and suggests that EIS may have the ability to predict future AD development.

Breastfeeding and the major fermentation metabolite lactate determine occurrence of Peptostreptococcaceae in infant feces.

Previous studies indicated an intrinsic relationship between infant diet, intestinal microbiota composition and fermentation activity with a strong focus on the role of breastfeeding on microbiota composition. Yet, microbially formed short-chain fatty acids acetate, propionate and butyrate and other fermentation metabolites such as lactate not only act as substrate for bacterial cross-feeding and as mediators in microbe-host interactions but also confer antimicrobial activity, which has received considerably less attention in the past research. It was the aim of this study to investigate the nutritional-microbial interactions that contribute to the development of infant gut microbiota with a focus on human milk oligosaccharide (HMO) fermentation. Infant fecal microbiota composition, fermentation metabolites and milk composition were analyzed from 69 mother-infant pairs of the Swiss birth cohort Childhood AlleRgy nutrition and Environment (CARE) at three time points depending on breastfeeding status defined at the age of 4 months, using quantitative microbiota profiling, HPLC-RI and 1H-NMR. We conducted in vitro fermentations in the presence of HMO fermentation metabolites and determined the antimicrobial activity of lactate and acetate against major Clostridiaceae and Peptostreptococcaceae representatives. Our data show that fucosyllactose represented 90% of the HMOs present in breast milk at 1- and 3-months post-partum with fecal accumulation of fucose, 1,2-propanediol and lactate indicating fermentation of HMOs that is likely driven by Bifidobacterium. Concurrently, there was a significantly lower absolute abundance of Peptostreptococcaceae in feces of exclusively breastfed infants at 3 months. In vitro, lactate inhibited strains of Peptostreptococcaceae. Taken together, this study not only identified breastfeeding dependent fecal microbiota and metabolite profiles but suggests that HMO-derived fermentation metabolites might exert an inhibitory effect against selected gut microbes.

The abundance of Ruminococcus bromii is associated with faecal butyrate levels and atopic dermatitis in infancy.

BACKGROUND: Impaired microbial development and decreased levels of short chain fatty acids, particularly butyrate, is suggested to have a role in the development of atopic dermatitis (AD). METHODS: Faecal microbiota composition, abundance of selected bacterial groups and fermentation metabolites were compared at 90, 180 and 360 days of life between 27 children who developed AD by age one (AD group), and 39 controls (non-AD group) among the CARE (Childhood AlleRgy, nutrition and Environment) study cohort. RESULTS: Diversity within the Firmicutes and Bacteroidetes phylum in the faecal microbiota was lower in the AD group compared to the non-AD group. Longitudinal analysis showed multiple amplicon sequence variants (ASV) within the same bacterial family to be differentially abundant. Namely, Ruminococcus bromii, a keystone primary starch degrader, and Akkermansia muciniphila, a mucin-utilizer, had lower abundance among the AD group. Children with AD were less likely to have high levels of faecal butyrate at 360 days compared to those without AD (11.5% vs 34.2%). At 360 days, children with high abundance of R. bromii had higher level of butyrate as well as lower proportion of children with AD compared to children with low abundance of R. bromii (11.1-12.5% vs 44.4-52.5%), which was independent of the abundance of the major butyrate producers. CONCLUSION: Our results suggested that R. bromii and other primary degraders might play an important role in the differences in microbial cross-feeding and metabolite formation between children with and without AD, which may influence the risk of developing the disease.

Natural mutation in the regulatory gene (srrG) influences virulence-associated genes and enhances invasiveness in Streptococcus dysgalactiae subsp. equisimilis strains isolated from cases of streptococcal toxic shock syndrome.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) has emerged as an important cause of severe invasive infections including streptococcal toxic shock syndrome (STSS). The present study aimed to identify genes involved in differences in invasiveness between STSS and non-invasive SDSE isolates. METHODS: STSS and non-invasive SDSE isolates were analysed to identify csrS/csrR mutations, followed by a comparative analysis of genomic sequences to identify mutations in other genes. Mutant strains were generated to examine changes in gene expression profiles and altered pathogenicity in mice. FINDINGS: Of the 79 STSS-SDSE clinical isolates, 15 (19.0%) harboured csrS/csrR mutations, while none were found in the non-invasive SDSE isolates. We identified a small RNA (sRNA) that comprised three direct repeats along with an inverted repeat and was transcribed in the same direction as the sagA gene. The sRNA was referred to as srrG (streptolysin S regulatory RNA in GGS). srrG mutations were identified in the STSS-SDSE strains and were found to be associated with elevated expression of the streptolysin S (SLS) gene cluster and enhanced pathogenicity in mice. INTERPRETATION: The csrS/csrR and srrG mutations that increased virulence gene expression in STSS-SDSE isolates were identified, and strains carrying these mutations caused increased lethality in mice. A significantly higher frequency of mutations was observed in STSS-SDSE isolates, thereby highlighting their importance in STSS. FUNDING: Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science (JSPS), and the Ministry of Health, Labor, and Welfare of Japan.

Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2  = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.

Molecular characterization and antimicrobial resistance of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2013 to 2018.

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and puerperal sepsis and shows high mortality. Its primary cause is group A streptococcus (GAS, Streptococcus pyogenes). In this study, we genotyped the cell-surface M virulence protein gene (emm) from 621 GAS isolates obtained from patients with STSS in Japan in 2013-2018 and performed antimicrobial susceptibility testing using the broth microdilution method. The predominant emm type was found to be 1, followed by 89, 12, and 3, which were identified in more than 70 % of STSS isolates. The proportions of emm3 and emm89 increased from 2.4 % and 12.0 %, respectively, during 2010-2012 to 5.6 % and 23.3 % during 2013-2018. In contrast, the proportion of emm1 decreased from 60.6 % to 39.3 % during the same two periods. Some emm types showed increasing proportions and were not isolated from patients with STSS in 2010-2012. Among these, an emm76 type increased in prevalence and was not included in the 30-valent M protein-based vaccine. Continual investigation of changes in the epidemiology of GAS which causes STSS can provide useful monitoring information such as future vaccination strategies and the emergence status of antimicrobial-resistant bacteria.

Surface Doping of Organic Single-Crystal Semiconductors to Produce Strain-Sensitive Conductive Nanosheets.

A highly periodic electrostatic potential, even though established in van der Waals bonded organic crystals, is essential for the realization of a coherent band electron system. While impurity doping is an effective chemical operation that can precisely tune the energy of an electronic system, it always faces an unavoidable difficulty in molecular crystals because the introduction of a relatively high density of dopants inevitably destroys the highly ordered molecular framework. In striking contrast, a versatile strategy is presented to create coherent 2D electronic carriers at the surface of organic semiconductor crystals with their precise molecular structures preserved perfectly. The formation of an assembly of redox-active molecular dopants via a simple one-shot solution process on a molecularly flat crystalline surface allows efficient chemical doping and results in a relatively high carrier density of 1013 cm-2 at room temperature. Structural and magnetotransport analyses comprehensively reveal that excellent carrier transport and piezoresistive effects can be obtained that are similar to those in bulk crystals.

Correlation between the static and dynamic responses of organic single-crystal field-effect transistors.

Transistors, the most important logic elements, are maintained under dynamic influence during circuit operations. Practically, circuit design protocols and frequency responsibility should stem from a perfect agreement between the static and dynamic properties. However, despite remarkable improvements in mobility for organic semiconductors, the correlation between the device performances achieved under static and dynamic circumstances is controversial. Particularly in the case of organic semiconductors, it remains unclear whether parasitic elements that relate to their unique molecular aggregates may violate the radiofrequency circuit model. Thus, we herein report the manufacture of micrometre-scale transistor arrays composed of solution-processed organic semiconductors, which achieve near very high-frequency band operations. Systematic investigations into the device geometrical factors revealed that the radiofrequency circuit model established on a solid-state continuous medium is extendable to organic single-crystal field-effect transistors. The validity of this radiofrequency circuit model allows a reliable prediction of the performances of organic radiofrequency devices.

The prevalence of oral symptoms caused by Rosaceae fruits and soybean consumption in children; a Japanese population-based survey.

BACKGROUND: Pollen food Syndrome (PFS) to Rosaceae fruits and soybean, related to Bet v 1 homologue sensitization has been reported increasingly throughout Japan, possibly due to the wide distribution of alder. METHODS: In 2015, we conducted a school-based questionnaire survey among two age groups; students in primary school (Years 1-2) and secondary school (Years 8-9) from each of the 47 prefectures of Japan. We analyzed the prevalence, demographic and clinical characteristics of children with oral symptoms to Rosaceae fruits/soybean; defined as oral symptoms occurring shortly after ingesting apple, peach, cherry or soybean. Additionally, we assessed the correlation between the prevalence and external data on alder sensitization rates by prefecture. RESULTS: Responses from 41,264 primary and 35,302 secondary school students were analyzed. The prevalence of oral symptoms to Rosaceae fruits/soybean was 0.99%, 95%CI: 0.89-1.09% and 2.75%, 95%CI: 2.59-2.93% among each age group, respectively. Children with oral symptoms were more likely to have parental and personal history of allergic disease compared to those without symptoms. Oral symptoms were experienced more often in children with severe spring allergic rhinitis or have both allergic rhinitis and wheeze. There was a strong correlation between the prevalence of oral symptoms and alder sensitization rates by prefecture among both age groups (r = 0.63, p < 0.001 and r = 0.76, p < 0.001, respectively). CONCLUSIONS: Oral symptoms to Rosaceae fruits/soybean, which is suggestive of PFS was reported by 1-3% Japanese school children. It was associated with the geographic alder sensitization rate, supporting the underlying sensitization to Bet v 1.

Damage-free Metal Electrode Transfer to Monolayer Organic Single Crystalline Thin Films.

Solution-processed organic thin film transistors (OTFTs) are an essential building block for next-generation printed electronic devices. Organic semiconductors (OSCs) that can spontaneously form a molecular assembly play a vital role in the fabrication of OTFTs. OTFT fabrication processes consist of sequential deposition of functional layers, which inherently brings significant difficulties in realizing ideal properties because underlayers are likely to be damaged by application of subsequent layers. These difficulties are particularly prominent when forming metal contact electrodes directly on an OSC surface, due to thermal damage during vacuum evaporation and the effect of solvents during subsequent photolithography. In this work, we demonstrate a simple and facile technique to transfer contact electrodes to ultrathin OSC films and form an ideal metal/OSC interface. Photolithographically defined metal electrodes are transferred and laminated using a polymeric bilayer thin film. One layer is a thick sacrificial polymer film that makes the overall film easier to handle and is water-soluble for dissolution later. The other is a thin buffer film that helps the template adhere to a substrate electrostatically. The present technique does not induce any fatal damage in the substrate OSC layers, which leads to successful fabrication of OTFTs composed of monolayer OSC films with a mobility of higher than 10 cm2 V-1 s-1, a subthreshold swing of less than 100 mV decade-1, and a low contact resistance of 175 Ω⋅cm. The reproducibility of efficient contact fabrication was confirmed by the operation of a 10 × 10 array of monolayer OTFTs. The technique developed here constitutes a key step forward not only for practical OTFT fabrication but also potentially for all existing vertically stacked organic devices, such as light-emitting diodes and solar cells.

Escherichia coli O8:H8 Carrying a Novel Variant of the Heat-Labile Enterotoxin LT2 Gene Caused Outbreaks of Diarrhea.

No outbreaks caused by Escherichia coli-producing heat-labile enterotoxin LT2 have been reported to date. Here, we revealed that the E. coli O8:H8 strains isolated from patients in 2 independent diarrhea outbreaks were negative for any known virulence determinants in routine microbiological tests, were very closely related, and carried a prophage-encoded gene for a novel LT2 variant (LT2d) and the genes for colonization factor antigen III. We also showed that LT2d has a cytotonic activity similar to LT1. These data indicate the importance of E. coli strains producing LT2d as a human pathogen.

Nationwide survey of the prevalence of wheeze, rhino-conjunctivitis, and eczema among Japanese children in 2015.

BACKGROUND: Global surveys and cohort studies have been conducted to evaluate the prevalence of allergic disease in childhood, but only a few nationwide surveys have been conducted in Japan. We aimed to report the prevalence of childhood allergic disease in Japan and determine the prevalence distribution by sex and prefecture. METHODS: In 2015, we conducted a school-based questionnaire survey using the Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire among two age groups: primary school students (PS, 6-8 years old) and middle school students (MS, 13-15 years old). The schools were randomly selected from each prefecture. RESULTS: Valid responses were obtained from 42,582 PS and 36,638 MS. Among PS and MS, the prevalence of wheeze was 10.2% and 8.2%, that of allergic rhino-conjunctivitis was 18.7% and 26.7%, and that of eczema was 14.6% and 9.7%, respectively. In terms of sex, the prevalence of wheeze and rhino-conjunctivitis was higher in male PS while that of rhino-conjunctivitis and eczema was higher in female MS. In terms of prefecture, there was a two-fold difference in the prevalence of wheeze and eczema and a four-fold difference in the prevalence of rhino-conjunctivitis, with each disease showing different distribution patterns. CONCLUSIONS: We demonstrated the prevalence of allergic disease among PS and MS in 2015. The prevalence tended to be higher in male PS and female MS. Each disease exhibited different prevalence ranges and distributions. Identifying the factors behind these differences is a topic for future research.

High-performance, semiconducting membrane composed of ultrathin, single-crystal organic semiconductors.

Thin film transistors (TFTs) are indispensable building blocks in any electronic device and play vital roles in switching, processing, and transmitting electronic information. TFT fabrication processes inherently require the sequential deposition of metal, semiconductor, and dielectric layers and so on, which makes it difficult to achieve reliable production of highly integrated devices. The integration issues are more apparent in organic TFTs (OTFTs), particularly for solution-processed organic semiconductors due to limits on which underlayers are compatible with the printing technologies. We demonstrate a ground-breaking methodology to integrate an active, semiconducting layer of OTFTs. In this method, a solution-processed, semiconducting membrane composed of few-molecular-layer-thick single-crystal organic semiconductors is exfoliated by water as a self-standing ultrathin membrane on the water surface and then transferred directly to any given underlayer. The ultrathin, semiconducting membrane preserves its original single crystallinity, resulting in excellent electronic properties with a high mobility up to 12 [Formula: see text] The ability to achieve transfer of wafer-scale single crystals with almost no deterioration of electrical properties means the present method is scalable. The demonstrations in this study show that the present transfer method can revolutionize printed electronics and constitute a key step forward in TFT fabrication processes.

T serotyping of group a streptococcus isolated from patients with pharyngitis or streptococcal toxic shock syndrome in Japan between 2005 and 2017.

Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017. The most prevalent T serotype from pharyngitis isolates was T12, followed by T1, T4, and TB3264. The most prevalent T serotype from STSS isolates was T1, followed by TB3264. Trend of increase and decrease in the frequency of T1 or TB3264 isolation from pharyngitis was correlated with that of STSS patients. The increase of T1 or TB3264 strain-infection in pharyngitis patients may increase the probability of causing STSS, indicating that careful monitoring of GAS serotypes is essential for the prediction of rapid increase of STSS in time to develop effective management strategies.

Fast-acting bactericidal activity of olanexidine gluconate against qacA/B-positive methicillin-resistant Staphylococcus aureus.

The qacA/B gene is one of the major determinants of resistance to antiseptics in methicillin-resistant Staphylococcus aureus (MRSA). Here, we compared the fast-acting bactericidal activity of skin antiseptics, including olanexidine gluconate (OLG), a new biguanide antiseptic agent introduced in Japan, against clinical qacA/B-positive MRSA strains by determination of minimum bactericidal concentration and time-kill assay. Our findings provide, for the first time, data indicating that the fast-acting bactericidal activity of OLG against qacA/B-positive MRSA is higher than that of chlorhexidine gluconate, even though both are biguanide antiseptics.

Children with East Asian-Born Parents Have an Increased Risk of Allergy but May Not Have More Asthma in Early Childhood.

BACKGROUND: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development. OBJECTIVE: To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents. METHODS: A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis. RESULTS: Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. Children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6, irrespective of ancestry. CONCLUSIONS: Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry.