Associations of gut microbiota features and circulating metabolites with systemic inflammation in children.

OBJECTIVE: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children. METHODS: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years. We examined associations of microbial taxa and metabolites-examining microbe-dependent and non-microbe-dependent metabolites separately-with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker. RESULTS: Of 335 taxa tested, 149 were associated (qFDR<0.05) with at least one inflammatory marker; 10 of these were robust to pseudocount choice. Several bacterial taxa involved in tryptophan metabolism were associated with inflammation, including kynurenine-degrading Ruminococcus, which was inversely associated with all inflammation markers. Of 1037 metabolites tested, 315 were previously identified as microbe dependent and were more frequently associated with PAI-1 and the InfSc than non-microbe dependent metabolites. In total, 87 metabolites were associated (qFDR<0.05) with at least one inflammation marker, including kynurenine (positively), serotonin (positively), and tryptophan (inversely). CONCLUSION: A distinct set of gut microbes and microbe-dependent metabolites, including those involved in the tryptophan-kynurenine-serotonin pathway, may be implicated in inflammatory pathways in childhood.

Plant-based diets and the gut microbiome: findings from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Mounting evidence indicates that although some plant-based diets are healthful, others are not. Changes in the gut microbiome and microbiome-dependent metabolites, such as trimethylamine N-oxide (TMAO), may explain differential health effects of plant-based diets. However, human data are sparse on whether qualitatively distinct types of plant-based diets differentially affect gut microbiome diversity, composition, particularly at the species level, and/or metabolites. OBJECTIVES: We aimed to examine cross-sectional associations of different plant-based indices with adult gut microbiome diversity, composition, and the metabolite TMAO. METHODS: We studied 705 adults in the Baltimore Longitudinal Study of Aging with data for diet, fecal microbiome (shotgun metagenomic sequencing), and key covariates. We derived healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) using data from food frequency questionnaires. We examined plant-based diet indices with microbiome α-diversity (richness and evenness measures), ß-diversity (Bray-Curtis and UniFrac measures), composition (species level), and plasma TMAO. We used regression models to determine associations before and after adjustment for age, sex, education, physical activity, smoking status, body mass index, and total energy intake. RESULTS: The analytic sample (mean age, 71.0 years, SD = 12.8 years) comprised 55.6% female and 67.5% non-Hispanic White participants. hPDI was positively and uPDI negatively associated with microbiome α-diversity, driven by microbial evenness (Pielou P < 0.05). hPDI was also positively associated with relative abundance of 3 polysaccharide-degrading bacterial species (Faecalibacterium prausnitzii, Eubacterium eligens, and Bacteroides thetaiotaomicron) and inversely associated with 6 species (Blautia hydrogenotrophica, Doreasp CAG 317, Eisenbergiella massiliensis, Sellimonas intestinalis, Blautia wexlerae, and Alistipes shahii). Furthermore, hPDI was inversely associated with TMAO. Associations did not differ by age, sex, or race. CONCLUSIONS: Greater adherence to a healthful plant-based diet is associated with microbiome features that have been linked to positive health; adherence to an unhealthful plant-based diet has opposing or null associations with these features.

Mother's age at menarche is associated with odds of preterm delivery: A case-control study.

OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD. DESIGN: A case-control study. SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts. POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls). METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined. MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records. RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years. CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.

Diet-Related and Gut-Derived Metabolites and Health Outcomes: A Scoping Review.

We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case-control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations.

Increases in Circulating and Fecal Butyrate are Associated With Reduced Blood Pressure and Hypertension: Results From the SPIRIT Trial.

Background Short chain fatty acids (SCFAs) are microbially derived end products of dietary fiber fermentation. The SCFA butyrate reduces blood pressure (BP) in mouse models. The association of SCFAs, including butyrate, with BP in humans is unclear, due in part to predominantly cross-sectional analyses and different biospecimens (blood versus fecal) for SCFA measurement. Longitudinal studies including both circulating and fecal SCFAs are lacking. Methods and Results We leveraged existing data from the SPIRIT (Survivorship Promotion In Reducing IGF-1 Trial), which randomized 121 adult cancer survivors with overweight/obesity to a behavioral weight-loss intervention, metformin, or self-directed weight-loss. Of participants with baseline serum and fecal SCFAs measured (n=111), a subset had serum (n=93) and fecal (n=89) SCFA measurements 12 months later. We used Poisson regression with robust error variance to estimate baseline associations of SCFAs with hypertension, and we assessed the percent change in SCFAs from baseline with corresponding 12-month changes in BP using multiple linear regression. Baseline fecal butyrate was inversely associated with prevalent hypertension (standardized PR [95%CI]: 0.71 [0.54, 0.92]). A 10% increase in fecal butyrate from baseline was associated with decreased systolic BP (ß [95%CI]: -0.56 [-1.01, -0.10] mm Hg), and a 10% increase in serum butyrate was associated with decreased systolic (ß [95%CI]: -1.39 [-2.15, -0.63] mm Hg) and diastolic (ß [95%CI]: -0.55 [-1.03, -0.08] mm Hg) BPs. Butyrate associations with systolic BP were linear and not modified by sex, race, or intervention arm. Conclusions Increased serum or fecal butyrate is associated with lowered BP. Butyrate may be a target for SCFA-centered BP-lowering interventions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02431676.

Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial.

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.

In Utero Exposure to Heavy Metals and Trace Elements and Childhood Blood Pressure in a U.S. Urban, Low-Income, Minority Birth Cohort.

BACKGROUND: In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations. OBJECTIVES: We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP. METHODS: We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured heavy metals and trace elements in maternal red blood cells collected 24-72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. RESULTS: Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: -11.51, -0.96) and 2.62 points lower with a doubling of Mn (95% CI: -5.20, -0.04). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (p-interaction=0.04). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn-child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: -18.03, -2.15), compared with a 1.49-point reduction (95% CI: -4.21, 1.24) in children whose mothers did not smoke during pregnancy (p-interaction=0.08). CONCLUSION: Se and Mn concentrations in maternal red blood cells collected 24-72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking-a source of Cd-during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood. https://doi.org/10.1289/EHP8325.

Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial.

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.

Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial.

CONTEXT: Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. DESIGN: Randomized, 3-parallel-arm controlled clinical trial. INTERVENTIONS AND OUTCOMES: Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. RESULTS: Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P < 0.0001), and -2.8% (P < 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months. CONCLUSIONS: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.

Associations Between Governor Political Affiliation and COVID-19 Cases, Deaths, and Testing in the U.S.

INTRODUCTION: The response to the COVID-19 pandemic became increasingly politicized in the U.S., and the political affiliation of state leaders may contribute to policies affecting the spread of the disease. This study examines the differences in COVID-19 infection, death, and testing by governor party affiliation across the 50 U.S. states and the District of Columbia. METHODS: A longitudinal analysis was conducted in December 2020 examining COVID-19 incidence, death, testing, and test positivity rates from March 15, 2020 through December 15, 2020. A Bayesian negative binomial model was fit to estimate the daily risk ratios and posterior intervals comparing rates by gubernatorial party affiliation. The analyses adjusted for state population density, rurality, Census region, age, race, ethnicity, poverty, number of physicians, obesity, cardiovascular disease, asthma, smoking, and presidential voting in 2020. RESULTS: From March 2020 to early June 2020, Republican-led states had lower COVID-19 incidence rates than Democratic-led states. On June 3, 2020, the association reversed, and Republican-led states had a higher incidence (risk ratio=1.10, 95% posterior interval=1.01, 1.18). This trend persisted through early December 2020. For death rates, Republican-led states had lower rates early in the pandemic but higher rates from July 4, 2020 (risk ratio=1.18, 95% posterior interval=1.02, 1.31) through mid-December 2020. Republican-led states had higher test positivity rates starting on May 30, 2020 (risk ratio=1.70, 95% posterior interval=1.66, 1.73) and lower testing rates by September 30, 2020 (risk ratio=0.95, 95% posterior interval=0.90, 0.98). CONCLUSIONS: Gubernatorial party affiliation may drive policy decisions that impact COVID-19 infections and deaths across the U.S. Future policy decisions should be guided by public health considerations rather than by political ideology.

Associations between governor political affiliation and COVID-19 cases, deaths, and testing in the United States.

INTRODUCTION: The response to the COVID-19 pandemic became increasingly politicized in the United States (US) and political affiliation of state leaders may contribute to policies affecting the spread of the disease. This study examined differences in COVID-19 infection, death, and testing by governor party affiliation across 50 US states and the District of Columbia. METHODS: A longitudinal analysis was conducted in December 2020 examining COVID-19 incidence, death, testing, and test positivity rates from March 15 through December 15, 2020. A Bayesian negative binomial model was fit to estimate daily risk ratios (RRs) and posterior intervals (PIs) comparing rates by gubernatorial party affiliation. The analyses adjusted for state population density, rurality, census region, age, race, ethnicity, poverty, number of physicians, obesity, cardiovascular disease, asthma, smoking, and presidential voting in 2020. RESULTS: From March to early June, Republican-led states had lower COVID-19 incidence rates compared to Democratic-led states. On June 3, the association reversed, and Republican-led states had higher incidence (RR=1.10, 95% PI=1.01, 1.18). This trend persisted through early December. For death rates, Republican-led states had lower rates early in the pandemic, but higher rates from July 4 (RR=1.18, 95% PI=1.02, 1.31) through mid-December. Republican-led states had higher test positivity rates starting on May 30 (RR=1.70, 95% PI=1.66, 1.73) and lower testing rates by September 30 (RR=0.95, 95% PI=0.90, 0.98). CONCLUSION: Gubernatorial party affiliation may drive policy decisions that impact COVID-19 infections and deaths across the US. Future policy decisions should be guided by public health considerations rather than political ideology.

Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease.

CONTEXT: Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. OBJECTIVE: To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD. DESIGN: Baseline assessment of longitudinal cohorts and randomized clinical trials. SETTING: Nonalcoholic Steatohepatitis Clinical Research Network. PATIENTS: Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States. MAIN OUTCOME MEASURES: We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression. RESULTS: Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features. CONCLUSIONS: Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.

Effects of high-fiber diets enriched with carbohydrate, protein, or unsaturated fat on circulating short chain fatty acids: results from the OmniHeart randomized trial.

BACKGROUND: Short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs. OBJECTIVES: We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet. METHODS: OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters. RESULTS: From baseline, serum acetate concentrations were increased by the Prot (ß: 0.24; 95% CI: 0.12, 0.35), Unsat (ß: 0.21; 95% CI: 0.10, 0.33), and Carb (ß: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (ß: -0.10; 95% CI: -0.16, -0.03) and Unsat (ß: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (ß: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05). CONCLUSIONS: Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT00051350.

Does cesarean delivery impact infant weight gain and adiposity over the first year of life?

BACKGROUND: Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode. METHODS: From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight. RESULTS: Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants. CONCLUSIONS: Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.

Asthma and the risk of type 2 diabetes in the Singapore Chinese Health Study.

AIM: Asthma is believed to increase the risk for several proinflammatory diseases, yet epidemiologic studies on asthma in relation to risk of developing type 2 diabetes are sparse and have reported inconsistent results. In the present study, we investigated the hypothesis that asthma is associated with an increased risk of incident type 2 diabetes in Chinese adults. METHODS: We used data from the Singapore Chinese Health Study, including Chinese men and women aged 45-74 years, free of cancer, heart disease, stroke, and diabetes at baseline (1993-1998) and followed through 2004 for incident physician-diagnosed diabetes. Cox regression models were used to examine the associations between self-reported history of physician-diagnosed asthma and risk of diabetes. RESULTS: During an average follow-up of 5.7 years per person, 2234 of the 42,842 participants included in the current analyses reported diagnoses of type 2 diabetes. After adjustment for potential confounders, not including body mass index (BMI), asthma was associated with a 31% increased risk of incident diabetes (HR=1.31; 95% CI: 1.00-1.72). The association was attenuated after adjustment for adult BMI (HR=1.25; 95% CI: 0.95-1.64). The asthma-diabetes association appeared stronger for adult- vs. child-diagnosed asthma cases, and for participants who were obese compared to non-obese. CONCLUSIONS: In Singaporean Chinese adults we observed a positive association between self-reported, physician-diagnosed asthma and risk of developing type 2 diabetes that was modestly attenuated by adjustment for BMI.

Age at menarche and cardiovascular disease mortality in Singaporean Chinese women: the Singapore Chinese Health Study.

PURPOSE: To examine whether age at menarche was inversely associated with cardiovascular disease (CVD) mortality in Singaporean Chinese women. METHODS: We followed prospectively 34,022 Chinese women aged 45 to 74 at enrollment (1993-1998), with complete data on study variables, through 2009 for primary cause of death from CVD, including coronary heart disease (CHD) and cerebrovascular disease (CERE). Hazard ratios (HRs) for CVD mortality were computed across menarcheal age categories and adjusted for potential confounders and body mass index. RESULTS: Over 460,374 person-years of follow-up, 1852 women died from CVD, 998 from CHD and 557 from CERE. There was a significant interaction between age at menarche and smoking (P < .05). In nonsmokers, age at menarche was inversely associated with risk for CVD and CHD mortality. HRs (and 95% confidence interval) for CVD mortality across menarcheal age categories (≤ 12, 13-14, 15-16, ≥ 17) were 1.06 (0.87-1.29), 1 (referent), 0.89 (0.79-1.00), and 0.80 (0.69-0.93), respectively (P(trend) < .001); HRs for CHD mortality were 1.06 (0.80-1.34), 1 (referent), 0.76 (0.65-0.90), and 0.72 (0.58-0.88), respectively (P(trend) < .001). Among nonsmokers, there was no association between age at menarche and CERE mortality. Among smokers, menarcheal age was not associated with CVD, CHD or CERE mortality. CONCLUSIONS: Menarcheal age was inversely associated with risk of CVD mortality in nonsmoking Chinese women.

Information channels associated with awareness of human papillomavirus infections and vaccination among Latino immigrants from safety net clinics.

We report on information channels associated with awareness about human papillomavirus (HPV) among immigrant Central and South American Latinos. We conducted a survey of 1,334 Latino ≥ 21 years attending safety-net clinics in 2007-2008. Logistic regression analyses evaluated associations with HPV awareness. Forty-eight percent were aware of HPV infection and 40% were aware of the vaccine. Spanish television (38%) and providers (23%) were the primary HPV information sources. Infection awareness was associated with internet use (OR 1.47; 95% CI 1.10-1.96) and self-efficacy to find health information (OR 1.19; 95% CI 1.08-1.30). Vaccine awareness was associated with media use for health information (OR 1.27; 95% CI 1.09-1.49) and internet use (OR 1.59; 95% CI 1.18-2.13). Although Spanish television has reached this low HPV awareness group, there may be missed opportunities for education by providers. Television and the internet may also be effective channels for future interventions.

Efficiency and cost-effectiveness of recruitment methods for male Latino smokers.

Little is known about the most effective strategies to recruit male Latino smokers to cessation research studies. The purpose of this study was to identify efficient and cost-effective research recruitment strategies for this priority population.

Soft drink and juice consumption and risk of pancreatic cancer: the Singapore Chinese Health Study.

BACKGROUND: Sugar-sweetened carbonated beverages (called soft drinks) and juices, which have a high glycemic load relative to other foods and beverages, have been hypothesized as pancreatic cancer risk factors. However, data thus far are scarce, especially from non-European descent populations. We investigated whether higher consumption of soft drinks and juice increases the risk of pancreatic cancer in Chinese men and women. METHODS: A prospective cohort analysis was done to examine the association between soft drink and juice consumption and the risk of pancreatic cancer in 60,524 participants of the Singapore Chinese Health Study with up to 14 years of follow-up. Information on consumption of soft drinks, juice, and other dietary items, as well as lifestyle and environmental exposures, was collected through in-person interviews at recruitment. Pancreatic cancer cases and deaths were ascertained by record linkage of the cohort database with records of population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths. RESULTS: The first 14 years for the cohort resulted in cumulative 648,387 person-years and 140 incident pancreatic cancer cases. Individuals consuming > or = 2 soft drinks/wk experienced a statistically significant increased risk of pancreatic cancer (hazard ratio, 1.87; 95% confidence interval, 1.10-3.15) compared with individuals who did not consume soft drinks after adjustment for potential confounders. There was no statistically significant association between juice consumption and risk of pancreatic cancer. CONCLUSION: Regular consumption of soft drinks may play an independent role in the development of pancreatic cancer.