Gut microbiome in the first 1000 days and risk for childhood food allergy.

Objective: To summarize recent data on the association between gut microbiome composition and food allergy (FA) in early childhood and highlight potential host-microbiome interactions that reinforce or abrogate oral tolerance.

Data Sources: PubMed search of English-language articles related to FA, other atopic disease, and the gut microbiome in pregnancy and early childhood.

Study Selections: Human studies published after 2015 assessing the relationship between the gut bacteriome and virome in the first 2 years of life and FA or food sensitization development in early childhood were prioritized.

Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants.

Background: The Short-Term Topical Application for Prevention of Atopic Dermatitis (STOP AD) study, a randomized, open-label trial evaluating the effect of short-term (from the first 4 postnatal days to age 8 weeks) skin barrier protection using Aveeno Dermexa Fast & Long-Lasting Balm (Johnson & Johnson, New Brunswick, NJ) in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of atopic dermatitis (AD) at age 12 months.

Objective: In the STOP AD study, we aimed to identify skin biomarkers that are associated with risk of development of AD.

Methods: Skin swabs were collected from the cheek and antecubital fossa (AF) at baseline, age 8 weeks, and age 12 months from subsets of study participants from the intervention arm (n = 43 of 119) and control arm (n = 43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, human β-defensin-1 [hBD-1], IL-18, IL-8, IL-1α, IL-1 receptor antagonist [IL-1RA], IL-1β, S100A8/9, and IL-36γ) by ELISA.

Skin surface biomarkers are associated with future development of atopic dermatitis in children with family history of allergic disease.

Background: Atopic dermatitis (AD) is a common childhood chronic inflammatory skin disorder that can significantly impact quality of life and has been linked to the subsequent development of food allergy, asthma, and allergic rhinitis, an association known as the "atopic march."

Objective: The aim of this study was to identify biomarkers collected non-invasively from the skin surface in order to predict AD before diagnosis across a broad age range of children.

Methods: Non-invasive skin surface measures and biomarkers were collected from 160 children (3-48 months of age) of three groups: (A) healthy with no family history of allergic disease, (B) healthy with family history of allergic disease, and (C) diagnosed AD.

Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes.

In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven.

Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe.

Prevention of childhood-onset type 1 diabetes has become more urgent with its marked increased incidence in recent decades in the modern world. Temporally associated with the rising incidence of type 1 diabetes, as well as other autoimmune and allergic diseases in childhood in modern times, is the disappearance of Bifidobacterium and specifically Bifidobacterium longum subsp. infantis (B.

Type 1 Diabetes: Disease Stratification.

Type 1 diabetes, a disorder characterized by immune-mediated loss of functional pancreatic beta cells, is a disease continuum with specific presymptomatic stages with defined risk of progression to symptomatic disease. Prognostic biomarkers have been developed for disease staging and for stratification of subjects that address the heterogeneity in rate of disease progression. Using biomarkers for stratification of subjects at different stages of type 1 diabetes will enable smaller and shorter intervention clinical trials with greater effect size.

Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis.

The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps.

JDRF's vision and strategy for prevention of type 1 diabetes.

The increasing incidence and lower threshold of developing type 1 diabetes (T1D) increases the urgency of its prevention. Insights from past and current natural history studies have provided the framework for a compelling strategy for primary and secondary prevention. Primary prevention of T1D should target the general childhood population with vaccines (viral or tolerogenic) or by altering microbiota-induced immunoregulation.

American Diabetes Association and JDRF Research Symposium: Diabetes and the Microbiome.

From 27-29 October 2014, more than 100 people gathered in Chicago, IL, to participate in a research symposium titled "Diabetes and the Microbiome," jointly sponsored by the American Diabetes Association and JDRF. The conference brought together international scholars and trainees from multiple disciplines, including microbiology, bioinformatics, endocrinology, metabolism, and immunology, to share the current understanding of host-microbe interactions and their influences on diabetes and metabolism. Notably, this gathering was the first to assemble specialists with distinct expertise in type 1 diabetes, type 2 diabetes, immunology, and microbiology with the goal of discussing and defining potential pathophysiologies linking the microbiome and diabetes.

Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association.

Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.

General population screening for type 1 diabetes: has its time come?

Purpose Of Review: The purpose of this review was to describe the potential for general childhood population-based screening of risk of symptomatic type 1 diabetes (T1D) RECENT FINDINGS: The earliest stages of T1D can be identified and risk and rate of progression to symptomatic disease can be estimated by the presence of multiple islet autoantibodies and glucose intolerance (dysglycemia) in individuals screened for risk. Screening for human leukocyte antigen risk genotypes in neonates with follow-up detection of islet autoantibodies in childhood has been explored. An alternative approach of general childhood population-based detection of autoantibodies at well child visits provides an approach to detect a high proportion of children who will develop T1D.

Protein kinase C-associated kinase regulates NF-κB activation through inducing IKK activation.

Activation of the transcription factor NF-κB induced by extracellular stimuli requires IKKα and IKKβ kinase activity. How IKKα and IKKβ are activated by various upstream signaling molecules is not fully understood. We previously showed that protein kinase C-associated kinase (PKK, also known as DIK/RIP4), which belongs to the receptor-interacting protein (RIP) kinase family, mediates the B cell activating factor of the TNF family (BAFF)-induced NF-κB activation in diffuse large B cell lymphoma (DLBCL) cell lines.

Delivering on George Eisenbarth's visionary pursuit of understanding pathogenesis and prevention of type 1 diabetes.

George Eisenbarth's pioneering and visionary research has provided a critical foundation that will be built on in the years ahead as we progress toward prevention of type 1 diabetes. His almost 30-year old model that type 1 diabetes was a chronic and predictable autoimmune disease with multiple identifiable progressive stages with a potential for interventions to prevent progression to symptomatic diabetes has stood the test of time. To deliver on the Eisenbarth vision and his "unfinished journey," the field needs: (1) to improve detection of risk of type 1 diabetes, (2) to improve staging and prediction of progression, (3) to perform smaller, shorter, practical, and an increased number of prevention clinical trials, and (4) to increase awareness of the potential for risk detection, staging, and prevention of type 1 diabetes and benefit/risk of prevention.

Mad1 is a transcriptional repressor of Bcl-6.

Bcl-6, a major regulator of B lymphocyte function that contributes to neoplastic transformation of B cells, is expressed in activated germinal center (GC) B cells and down-regulated during terminal differentiation to plasma cells. Regulation of Bcl-6 expression is incompletely characterized. Terminal B cell differentiation is associated with down-regulation of Bcl-6, activation of Blimp-1, modulation of Myc, and specifically with the up-regulation of the Mad1 and Mad4 transcription factors, which play a critical role in cell differentiation and cell cycle regulation.

Human embryonic stem cell research and the Juvenile Diabetes Research Foundation International - a work in progress.

The Juvenile Diabetes Research Foundation International (JDRF) was founded in 1970 by parents of children with juvenile diabetes to find a cure for diabetes and its complications through the support of research. The foundation was an early supporter of stem cell research, recognizing the promise of stem cells to quicken the pace of discovery for a cure for juvenile diabetes. The JDRF has committed considerable resources to supporting stem cell research in both the United States and abroad.

Activation of terminal B cell differentiation by inhibition of histone deacetylation.

A role for histone acetylation, which can alter the accessibility of DNA to transcriptional regulatory proteins and contribute to gene expression, in regulating terminal B cell differentiation was investigated in the mature B lymphoma L10A and mouse splenic B cells. Incubation of the L10A cells with the histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and butyrate increased expression of Blimp-1, J chain, and mad genes, decreased expression of c-myc and BSAP/Pax-5 genes, increased the expression of surface CD43 and Syndecan-1, and decreased surface IgM. Incubation of splenic B cells with TSA and dextran conjugated anti-IgD Ab increased Blimp-1 gene and Syndecan-1 surface expression.