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Background In animal models, prenatal zinc deficiency induced epigenetic changes in the fetus, but data in humans are lacking. We aimed to examine associations between maternal zinc levels during pregnancy and DNA methylation in LINE-1 and Alu repetitive sequences in young adult offspring, as well as anthropometry and cardiometabolic parameters. Methods Participants were 74 pregnant women from the Chiang Mai Low Birth Weight cohort, and their offspring followed up at 20 years of age. Maternal plasma zinc concentrations were measured at approximately 36 weeks of gestation. DNA methylation levels in LINE-1 and Alu repetitive sequences were measured in the offspring, as well as anthropometry and cardiometabolic parameters (lipid profile, blood pressure, and glucose metabolism). Results Over half of mothers (39/74; 53%) were zinc deficient (< 50 mu g/ dL) during their third trimester of pregnancy. Maternal zinc concentrations during pregnancy were associated with LINE-1 DNA methylation levels in adult offspring. Specifically, lower prenatal zinc concentrations were associated with: 1) lower levels of total LINE-1 methylation; 2) lower levels of LINE-1 hypermethylation loci; and 3) higher levels of LINE-1 partial methylation loci. Prenatal zinc concentrations were not associated with Alu methylation levels, nor with any anthropometric or cardiometabolic parameters in adult offspring. However, we observed associations between Alu and LINE-1 methylation patterns and cardiometabolic outcomes in offspring, namely total cholesterol levels and diastolic blood pressure, respectively. Conclusions Lower maternal zinc concentrations late in gestation were associated with changes in DNA methylation in later life. Thus, zinc deficiency during pregnancy may induce alterations in total LINE-1 methylation and LINE-1 hypermethylation loci. These results suggest a possible epigenetic link between zinc deficiency during pregnancy and long-term outcomes in the offspring.

Importance Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in