Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host–microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

Effects of diet on the childhood gut microbiome and its implications for atopic dermatitisTo the Editor:Atopic dermatitis (AD) is a common childhood disorder with significant reductions in the child's quality of life. The composition and diversity of the early gut microbiota has been linked to the development of atopic conditions including AD. 1 Although the prevalence of atopic diseases is lower in Africa, 2 individuals of African origin who live in Western countries are at a significantly higher risk for atopic conditions like AD and food allergy, and suffer from more severe allergic diseases than do their white counterparts, 3 possibly reflecting an enhanced genetic predisposition to allergy that is kept in check by their ancestral environment. 2 In certain areas of Africa, people still live in an environment enriched in microbes through close daily contact with animals and plants in natural settings. Therefore, determining how their natural environment or diet protects these potentially atrisk populations should shed light on causes of the global rise in allergic conditions. In this study, we characterized gut microbiotas of black South African (Xhosa) children from the remote rural Mqanduli district of the Eastern Cape in association with AD.Patients with AD were recruited from the Dermatology Department of the Nelson Mandela Academic Hospital in Umtata, in the Eastern Cape. Control (nonallergic, non-foodsensitized) subjects were recruited from the areas surrounding 10 district community health clinics. Detailed clinical data were gathered on all toddlers. The fecal microbiota of these children was analyzed and compared in relation to AD, other clinical variables, and their diet. For details, see this article's Methods section in the Online Repository at www.jacionline.org. This study was approved by the institutional review boards of the

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Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, blackcurrant supplementation decreased the loss of whole-body bone mineral density (BMD) compared to the control group (p < 0.05), though the improvement of whole-body BMD remained significant only in the high BC group (p < 0.05). Blackcurrant supplementation also led to a significant increase in serum amino-terminal propeptide of type 1 procollagen (P1NP), a marker of bone formation (p < 0.05). These findings suggest that daily consumption of 784 mg of blackcurrant powder for six months mitigates the risk of postmenopausal bone loss, potentially through enhancing bone formation. Further studies of larger samples with various skeletal conditions are warranted to confirm these findings.