Work has shown that increased exposure to air pollutants independently contributes to obesity and type 2 diabetes risk, yet the exact mechanisms underlying these associations have not been fully characterized. The current review summarizes recent findings regarding the impact of inhaled and ingested air pollutants on the gut microbiota. Animal and human studies provide evidence that air pollutants, such as particulate matter, nitrogen oxides, and ozone, have the potential to alter the gut microbiota. Further, studies suggest that such exposure-induced alterations to the gut microbiota may contribute to increased risk for obesity and type 2 diabetes through inflammatory pathways. Future work is needed to fully understand the complex interactions between air pollution, the gut microbiome, and human health. Additionally, advanced sequencing methods for gut microbiome research present unique opportunities to study the underlying pathways that link increased air pollution exposure with obesity and type 2 diabetes risk.

We aimed to determine if the newborn gut microbiota is an underlying determinant of early life growth trajectories. 132 Hispanic infants were recruited at 1-month postpartum. The infant gut microbiome was characterized using 16S rRNA amplicon sequencing. Rapid infant growth was defined as a weight-for-age z-score (WAZ) change greater than 0.67 between birth and 12-months of age. Measures of infant growth included change in WAZ, weight-for-length z-score (WLZ), and body mass index (BMI) z-scores from birth to 12-months and infant anthropometrics at 12-months (weight, skinfold thickness). Of the 132 infants, 40% had rapid growth in the first year of life. Multiple metrics of alpha-diversity predicted rapid infant growth, including a higher Shannon diversity (OR = 1.83; 95% CI: 1.07–3.29; p = .03), Faith’s phylogenic diversity (OR = 1.41, 95% CI: 1.05–1.94; p = .03), and richness (OR = 1.04, 95% CI: 1.01–1.08; p = .02). Many of these alpha-diversity metrics were also positively associated with increases in WAZ, WLZ, and BMI z-scores from birth to 12-months (p_all<0.05). Importantly, we identified subsets of microbial consortia whose abundance were correlated with these same measures of infant growth. We also found that rapid growers were enriched in multiple taxa belonging to genera such as Acinetobacter, Collinsella, Enterococcus, Neisseria, and Parabacteroides. Moreover, measures of the newborn gut microbiota explained up to an additional 5% of the variance in rapid growth beyond known clinical predictors (R² = 0.37 vs. 0.32, p < .01). These findings indicate that a more mature gut microbiota, characterized by increased alpha-diversity, at as early as 1-month of age, may influence infant growth trajectories in the first year of life.

Low serum total 25-hydroxyvitamin D₃ [25(OH)D₃] concentrations have been associated with cognitive impairment. However, it is unclear if serum 25(OH)D₃ concentrations are a valid indicator of the concentrations of vitamin D and its metabolites in human brain. The aim of this study was to develop and validate a method to quantify vitamin D₃, 25(OH)D₃, and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] in human brain. The assay developments were performed using porcine brains. Liquid extraction was used in homogenized samples (∼0.1 g each) prior to analysis by LC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione. This method was then applied to the determination of vitamin D and its metabolites in a whole human brain obtained from the National Development and Research Institutes. The method showed good linearity of vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ over the physiological range (R² = 0.9995, 0.9968, and 0.9970, respectively). The lowest detection limit for vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ in porcine brain was 25, 50 and 25 pg/g, respectively. The method was successfully applied to the determination of vitamin D₃ and its metabolites in the prefrontal cortex, middle frontal cortex, middle temporal cortex, cerebellum, corpus callosum, medulla, and pons of a human brain. All analyzed human brain regions contained 25(OH)D₃, with corpus callosum containing 334 pg/g compared with 158 pg/g in cerebellum. 1,25(OH)₂D₃ was only detected in prefrontal and middle frontal cortices at a very low level. No vitamin D₃ was detected in any examined areas of this single human brain. To the best of our knowledge, this study is the first report of the measurement of concentrations of vitamin D metabolites in human brain. This validated method can be applied to postmortem studies to obtain accurate information about the presence and role of vitamin D and its metabolites in human brain and neurodegenerative diseases.

Young-onset type 2 diabetes and prediabetes is a growing epidemic. Poor diet is a known risk factor for T2D in older adults, but the contribution of diet to risk factors for T2D is not well-described in youth. Our objective was to examine the relationship of diet quality with prediabetes, glucose regulation, and adiposity in young adults. A cohort of young adults (n = 155, age 17–22) was examined between 2014–2018, and 89 underwent a follow-up visit from 2020–2022. At each visit, participants completed diet and body composition assessments and an oral glucose tolerance test. Adherence to four dietary patterns was assessed: Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI), Mediterranean diet, and Diet Inflammatory Index (DII). Regression analyses were used to determine adjusted associations of diet with risk for prediabetes and adiposity. Each one-point increase in DASH or HEI scores between visits reduced the risk for prediabetes at follow-up by 64% (OR, 95% CI: 0.36, 0.17–0.68) and 9% (OR, 95% CI: 0.91, 0.85–0.96), respectively. The DASH diet was inversely associated with adiposity, while DII was positively associated with adiposity. In summary, positive changes in HEI and DASH scores were associated with reduced risk for prediabetes in young adults.

Ambient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults. Participants were 170 young adults (17-22 years) from the Meta-AIR cohort of the Children's Health Study (CHS). Residential AAP exposure (PM_2.5, PM₁₀, NO₂, 8-hour maximum O₃, redox-weighted oxidative capacity [O_x^wt]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by weighted gene correlation network analysis. The first principal component of each network represented its expression profile. Multivariable mixed effects regression models adjusted for sociodemographic, behavioral, and clinical covariates; baseline CHS town code was a random effect. Effects estimates are scaled to one standard deviation of exposure. Mediation analysis explored microRNA profiles as potential mediators of exposure-outcome associations. DIANA-mirPATH identified overrepresented gene pathways targeted by miRNA networks. Prior-month O_x^wt was associated with NAFLD (OR=3.45; p = 0.003) and inversely associated with microRNA Network A (β = -0.016; p = 0.026). Prior-year NO₂ was associated with non-HDL-cholesterol (β = 7.13; p = 0.01) and inversely associated with miRNA Network A (β = -0.019; p = 0.022). Network A expression was inversely associated with NAFLD (OR=0.35; p = 0.010) and non-HDL-C (β = -6.94 mg/dL; p = 0.035). Network A members miR-199a/b-3p and miR-130a, which both target fatty acid synthase, mediated 21% of the association between prior-month O_x^wt exposure with NAFLD (p = 0.048) and 23.3% of the association between prior-year NO₂ exposure and non-HDL-cholesterol (p = 0.026), respectively. Exposure to AAP may contribute to adverse lipid profiles and NAFLD risk among young adults via altered expression of microRNA profiles.

Exposure to ambient and near-roadway air pollution during pregnancy has been linked with several adverse health outcomes for pregnant women and their babies. Emerging research indicates that microRNA (miRNA) expression can be altered by exposure to air pollutants in a variety of tissues. Additionally, miRNAs from breast tissue and circulating miRNAs have previously been proposed as a biomarker for breast cancer diagnosis and prognosis. Therefore, this study sought to evaluate the associations between pregnancy exposures to ambient (PM₁₀, PM_2.5, NO₂, O₃) and near-roadway air pollution (total NO _x , freeway NO _x , non-freeway NO _x ) with breast milk extracellular vesicle miRNA (EV-miRNA), measured at 1-month postpartum, in a cohort of 108 Latina women living in Southern California. We found that PM₁₀ exposure during pregnancy was positively associated with hsa-miR-200c-3p, hsa-miR-200b-3p, and hsa-let-7c-5p, and was negatively associated with hsa-miR-378d. We also found that pregnancy PM_2.5 exposure was positively associated with hsa-miR-200c-3p and hsa-miR-200b-3p. First and second trimester exposure to PM₁₀ and PM_2.5 was associated with several EV-miRNAs with putative messenger RNA targets related to cancer. This study provides preliminary evidence that air pollution exposure during pregnancy is associated with human milk EV-miRNA expression.