Summary
The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut‐associated lymphoid ...tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age‐related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut‐associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short‐chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL‐10/TGF‐β dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the ‘sterile womb’ paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre‐ and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a ‘healthy gut microbiome’ that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks, using harmonized outcomes and methodologies, are needed to advance our understanding in this field.
Summary
Background
Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling.
Objective
We examined gut microbiome ...development in the first year of life in relation to innate immune responses and onset of IgE‐associated eczema over the first 2.5 years in predisposed children due to maternal atopy www.anzctr.org.au, trial ID ACTRN12606000280505.
Methods
Microbial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n = 10) who developed IgE‐associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n = 10). Microbiome data at 1 week and 1 month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age.
Results
The relative abundance of Gram‐positive Ruminococcaceae was lower at 1 week of age in infants developing IgE‐associated eczema, compared with controls (P = 0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL‐6 (−0.567, P = 0.042) and TNF‐α (−0.597, P = 0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram‐negative taxa) and TLR4‐induced TNF‐α (rs = −0.629, P = 0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4‐induced TNF‐α (rs = −0.697, P = 0.038) and Enterobacteriaceae and IL‐6 (rs = −0.709, P = 0.035). Mothers whose infants developed IgE‐associated eczema had lower α‐diversity of Bacteroidetes (P = 0.04) although this was not seen later in their infants. At 1 year, α‐diversity of Actinobacteria was lower in infants with IgE‐associated eczema compared with controls (P = 0.002).
Conclusion and clinical relevance
Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR‐ligands and subsequent development of IgE‐associated eczema.
• Mediterranean‐type ecosystems contain 20% of all vascular plant diversity on Earth and have been identified as being particularly threatened by future increases in drought. Of particular concern is ...the Cape Floral Region of South Africa, a global biodiversity hotspot, yet there are limited experimental data to validate predicted impacts on the flora. In a field rainout experiment, we tested whether rooting depth and degree of isohydry or anisohydry could aid in the functional classification of drought responses across diverse growth forms. • We imposed a 6‐month summer drought, for 2 yr, in a mountain fynbos shrubland. We monitored a suite of parameters, from physiological traits to morphological outcomes, in seven species comprising the three dominant growth forms (deep‐rooted proteoid shrubs, shallow‐rooted ericoid shrubs and graminoid restioids). • There was considerable variation in drought response both between and within the growth forms. The shallow‐rooted, anisohydric ericoid shrubs all suffered considerable reductions in growth and flowering and increased mortality. By contrast, the shallow‐rooted, isohydric restioids and deep‐rooted, isohydric proteoid shrubs were largely unaffected by the drought. • Rooting depth and degree of iso/anisohydry allow a first‐order functional classification of drought response pathways in this flora. Consideration of additional traits would further refine this approach.
Background
Long‐term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding ...Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age.
Methods
In a double‐blind placebo‐controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 108 CFU (n = 90) from 4–13 months of age. At age 8–9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO) was measured.
Results
Of 171 children that completed the intervention, 121 were assessed at age 8–9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group OR (95% CI) 0.62 (0.28–1.36). Corresponding numbers for IgE‐associated allergic disease were 9/53 (17%) vs 12/59 (20%) 0.80 (0.31–2.09). Median (25th‐75th percentile) FENO was 9 (8–12) in the probiotic vs 8 (7–12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05).
Conclusions
There was no long‐term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long‐term benefits a larger study population had been needed.
Summary
Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more ...affluent regions. Quantitatively, the largest important source of early immune‐microbial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ‘dysbiotic drift’ in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo‐controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high‐risk infants. It is however stressed that these recommendations are conditional, based on very low‐quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy‐preventive effects and enable future evidence‐based implementation.
Background
Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota ...development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.
Methods
Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.
Results
At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year‐olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).
Conclusions
We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.
Gut microbiota development was studied prospectively from infancy to school age in relation to onset of IgE‐associated allergic diseases. We also examined correlations between gut microbiota and T‐cell regulatory markers. We identified temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. In allergic 8‐year‐olds, Faecalibacterium correlated with polyclonally activated IL‐10 mRNA levels of peripheral blood mononuclear cells, with the same trend for FOXP3.
Abstract
In the first of a planned sequence of articles, we present a simple method for reconstructing radial density structures of the solar corona in the vicinity of the Parker Solar Probe (PSP) ...near and during perihelion passes. We describe how we model the apparent kinematics of stationary K-corona striae from the PSP Wide-field Imager for Parker Solar Probe (WISPR) viewpoint using a simple two-parameter model, form a partial basis of the data space that is a WISPR image sequence, and change the basis from image coordinates to “tomographic coordinates” in order to determine the parameters of such features. We apply the method to a simple three-dimensional model of a WISPR coronal flythrough, demonstrate the ways that it succeeds and fails, and discuss possible improvements to the sensitivity and applicability of the method for real WISPR data.
Abstract Background Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical ...features are absent and genetic variants of unknown significance (GVUS) in the α-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of > 12 mm), GLA GVUS and an uncertain diagnosis of FD. Methods A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined. Results A definite diagnosis of FD was defined as follows: a GLA mutation with ≤ 5% GLA activity (leucocytes, mean of reference value, males only) with ≥ 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso)Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT > 15 mm) < 20 years exclude FD. Other criteria were rejected due to insufficient evidence. Conclusions In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed.
The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration ...and with observationally based data sets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST data set. In the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is required to rectify this in future configurations.
•Toxicity of oil sands process water extract to fish determined (LC50 ∼8mgL−1).•Toxicity of esterifiable free naphthenic acids determined (LC50 5.4mgL−1).•Toxicity of ‘classical’ naphthenic acids ...determined (LC50 13.1mgL−1).•Toxicity of naphtheno-monoaromatic acids determined (LC50 8.1mgL−1).•Concentration range from no effect to 100% mortality<order of magnitude for all.
The toxicity of oil sands process-affected water (OSPW) has regularly been attributed to naphthenic acids, which exist in complex mixtures. If on remediation treatment (e.g., ozonation) or on entering the environment, the mixtures of these acids all behave in the same way, then they can be studied as a whole. If, however, some acids are resistant to change, whilst others are not, or are less resistant, it is important to establish which sub-classes of acids are the most toxic.
In the present study we therefore assayed the acute toxicity to larval fish, of a whole acidified OSPW extract and an esterifiable naphthenic acids fraction, de-esterified with alkali: both fractions were toxic (LC50 ∼5–8mgL−1). We then fractionated the acids by argentation solid phase extraction of the esters and examined the acute toxicity of two fractions: a de-esterified alicyclic acids fraction, which contained, for example, adamantane and diamantane carboxylic acids, and an aromatic acids fraction. The alicyclic acids were toxic (LC50 13mgL−1) but the higher molecular weight aromatic acids fraction was somewhat more toxic, at least on a weight per volume basis (LC50 8mgL−1; P<0.05) (for comparison, the monoaromatic dehydroabietic acid had a LC50 of ∼1mgL−1).
These results show how toxic naphthenic acids of OSPW are to these larval fish and that on a weight per volume basis, the aromatic acids are at least as toxic as the ‘classical’ alicyclic acids. The environmental fates and other toxic effects, if any, of the fractions remain to be established.
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