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OBJECTIVE To determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs). RESEARCH DESIGN AND METHODS We conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them ( n = 121) to either 1 ) metformin (up to 2,000 mg), 2 ) coach-directed behavioral weight loss, or 3 ) self-directed care (control) for 12 months. We collected stool and serum at baseline ( n = 114), 6 months ( n = 109), and 12 months ( n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. RESULTS Of the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia , including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole-genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate-producing pathway and three pathways in glucose metabolism. CONCLUSIONS Metformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin’s health effects.

Background Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants. Method In this prospective study (Nurture: recruitment 2013–2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months. Results Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05). Conclusions Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months. Electronic supplementary material The online version of this article (10.1186/s12941-019-0318-9) contains supplementary material, which is available to authorized users.

BackgroundPreeclampsia is a leading contributor to maternal and perinatal morbidity and mortality. In mice experiments, manganese (Mn) and selenium (Se) are protective whereas cadmium (Cd) is promotive for preeclampsia. Epidemiologic findings on these chemical elements have been inconsistent. To confirm experimental findings in mice, we examined associations of trace minerals (Mn and Se) and heavy metals (Cd, lead [Pb], and mercury [Hg]) with preeclampsia in a birth cohort.Methods and ResultsA total of 1274 women from the Boston Birth Cohort (enrolled since 1998) had complete data on the exposures and outcome. We measured Mn, Se, Cd, Pb, and Hg from red blood cells collected within 24 to 72 hours after delivery. We ascertained preeclampsia diagnosis from medical records. We used Poisson regression with robust variance models to estimate prevalence ratios (PRs) and 95% CIs. A total of 115 (9.0%) women developed preeclampsia. We observed evidence of a dose–response trend for Mn (P for trend<0.001) and to some extent for Cd (P for trend=0.009) quintiles. After multivariable adjustment, a 1 SD increment in Mn was associated with 32% lower risk of developing preeclampsia (PR=0.68; 95% CI, 0.54–0.86), whereas a 1 SD increment in Cd was associated with 15% higher risk of preeclampsia (PR=1.15; 95% CI, 0.98–1.36). Null associations were observed for Se, Pb, and Hg.ConclusionsFindings from our cohort, consistent with evidence from mice experiments and human studies, indicate that women with lower blood concentration of Mn or higher Cd are more likely to develop preeclampsia.

Exposure to ambient air pollution has been associated with greater risk of elevated blood pressure (BP) in adults and children. Recent evidence suggests that air pollution exposure in pregnancy may also portend increased risk for the next generation; however, few studies have examined this relationship. We conducted a prospective study of 1293 mothers in the Boston Birth Cohort (enrolled 1998-2012) and their children who had follow-up visits between 3 and 9 years of age and complete exposure and outcome data. Our primary exposure, ambient particulate matter ≤2.5 µm (PM) concentration during pregnancy, was estimated by matching mother's residential address to the US Environmental Protection Agency's air quality monitors. We defined our primary outcome child systolic BP (SBP) percentile according to US reference (Fourth Report) and classified elevated BP as SBP ≥90th percentile. Our multivariable-adjusted cubic spline showed a sharp increase in offspring SBP percentile and risk for elevated BP when third-trimester PM concentration was ≥13 μg/m The highest versus lowest tertile of third-trimester PM exposure was associated with a 4.85 (95% confidence interval: 1.38-8.37) percentile increase in child SBP or a 1.61 (95% confidence interval: 1.13-2.30) times higher risk of child elevated BP. A 5-μg/m increment in PM during the third trimester was associated with a 3.49 (95% confidence interval: 0.71-6.26) percentile increase in child SBP or a 1.47 (95% confidence interval: 1.17-1.85) times higher risk of elevated BP. Our findings suggest that exposure to ambient PM during the third trimester of pregnancy is associated with elevated BP in children, ages 3 to 9 years.