Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Background: Maternal vitamin D deficiency during pregnancy may affect fetal outcomes.Objective: The objective of this study was to examine whether mat

Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. In a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3–4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n–3 and n–6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: “MUFA and low SFA,” “high n–6 PUFA,” “high n–3 PUFA,” and “high medium-chain fatty acids.” In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the “high n–3 PUFA” pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n–6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n–6) and total n–3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the “high medium-chain fatty acid” pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. This study provides unique insights about the “normal” variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

The incidence of pediatric asthma has increased substantially in recent decades, reaching a worldwide prevalence of 14%. This rapid increase may be attributed to the loss of “Old Friend” microbes from the human microbiota resulting in a less diverse and “dysbiotic” gut microbiota, which fails to optimally stimulate immune development during infancy. This hypothesis is supported by observations that the gut microbiota is different in infants who develop asthma later in life compared to those who remain healthy. Thus, early life exposures that influence gut microbiota play a crucial role in asthma development. Breastfeeding is one such exposure; it is generally considered protective against pediatric asthma, although conflicting results have been reported, potentially due to variations in milk composition between individuals and across populations. Human milk oligosaccharides (HMOs) and milk microbiota are two major milk components that influence the infant gut microbiota and hence, development of the immune system. Among their many immunomodulatory functions, HMOs exert a selective pressure within the infant gut microbial niche, preferentially promoting the proliferation of specific bacteria including Bifidobacteria. Milk is also a source of viable bacteria originating from the maternal gut and infant oral cavity. As such, breastmilk has prebiotic and probiotic properties that can modulate two of the main forces controlling the gut microbial community assembly, i.e., dispersal and selection. Here, we review the latest evidence, mechanisms and hypotheses for the synergistic and/or additive effects of milk microbiota and HMOs in protecting against pediatric asthma.

Breastfeeding has many established health benefits, but its impact on asthma development is uncertain. Breastfeeding appears to have a positive and dose-dependent impact on respiratory health, particularly during early childhood and in high-risk populations; however, the strength and causality of these associations are unclear. It is challenging to compare results across studies due to methodological differences and biological variation. Resolving these inconsistencies will require well-designed, prospective studies that accurately capture asthma diagnoses and infant feeding exposures (including breastfeeding duration, exclusivity, and method of feeding), account for key confounders, evaluate dose effects, and consider effect modification and reverse causality. Mechanistic studies examining human milk bioactives and their impact on lung health and asthma development are beginning to emerge, and these will be important in establishing the causality and mechanistic basis of the observed associations between breastfeeding and asthma. In this review, we summarize current evidence on this topic, identify possible reasons for disagreement across studies, discuss potential mechanisms for a causal association, and provide recommendations for future research.