Association of Coffee and Tea Intake with the Oral Microbiome: Results from a Large Cross-Sectional Study.

Background: The oral microbiota play a central role in oral health, and possibly in carcinogenesis. Research suggests that coffee and tea consumption may have beneficial health effects. We examined the associations of these common beverages with the oral ecosystem in a large cross-sectional study.Methods: We assessed oral microbiota in mouthwash samples from 938 participants in two U.S. cohorts using 16S rRNA gene sequencing. Coffee and tea intake were assessed from food frequency questionnaires. We examined associations of coffee and tea intake with overall oral microbiota diversity and composition using linear regression and permutational MANOVA, respectively, and with taxon abundance using negative binomial generalized linear models; all models adjusted for age, sex, cohort, body mass index, smoking, ethanol intake, and energy intake.Results: Higher tea intake was associated with greater oral microbiota richness (P = 0.05) and diversity (P = 0.006), and shifts in overall community composition (P = 0.002); coffee was not associated with these microbiome parameters. Tea intake was associated with altered abundance of several oral taxa; these included Fusobacteriales, Clostridiales, and Shuttleworthia satelles (higher with increasing tea) and Bifidobacteriaceae, Bergeyella, Lactobacillales, and Kingella oralis (lower with increasing tea). Higher coffee intake was only associated with greater abundance of Granulicatella and Synergistetes.Conclusions: In the largest study to date of tea and coffee consumption in relation to the oral microbiota, the microbiota of tea drinkers differed in several ways from nondrinkers.Impact: Tea-driven changes to the oral microbiome may contribute to previously observed associations between tea and oral and systemic diseases, including cancers. Cancer Epidemiol Biomarkers Prev; 27(7); 814-21. ©2018 AACR.

Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Creatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. OBJECTIVE: We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. METHODS: Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 µg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 µg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. RESULTS: Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (ß = 0.30; 95% CI: 0.17, 0.43; P < 0.0001). CONCLUSIONS: Our findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556.

Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial.

BACKGROUND: The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)-contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. OBJECTIVES: Our aim was to determine whether 400 or 800 µg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in which 622 participants were randomized to receive 400 µg FA, 800 µg FA, 3 g creatine, 3 g creatine+400 µg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. RESULTS: Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-µg FA group exceeded that of the placebo group (weeks 1-12: ß= -0.09, 95% CI: -0.18, -0.01; weeks 13-24: FA continued: ß= -0.12, 95% CI: -0.24, -0.00; FA switched to placebo: ß= -0.14, 95% CI: -0.26, -0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. CONCLUSIONS: In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 µg (but not 400 µg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles.

Batch effects and pathway analysis: two potential perils in cancer studies involving DNA methylation array analysis.

BACKGROUND: DNA methylation microarrays have become an increasingly popular means of studying the role of epigenetics in cancer, although the methods used to analyze these arrays are still being developed and existing methods are not always widely disseminated among microarray users. METHODS: We investigated two problems likely to confront DNA methylation microarray users: (i) batch effects and (ii) the use of widely available pathway analysis software to analyze results. First, DNA taken from individuals exposed to low and high levels of drinking water arsenic were plated twice on Illumina's Infinium 450 K HumanMethylation Array, once in order of exposure and again following randomization. Second, we conducted simulations in which random CpG sites were drawn from the 450 K array and subjected to pathway analysis using Ingenuity's IPA software. RESULTS: The majority of differentially methylated CpG sites identified in Run One were due to batch effects; few sites were also identified in Run Two. In addition, the pathway analysis software reported many significant associations between our data, randomly drawn from the 450 K array, and various diseases and biological functions. CONCLUSIONS: These analyses illustrate the pitfalls of not properly controlling for chip-specific batch effects as well as using pathway analysis software created for gene expression arrays to analyze DNA methylation array data. IMPACT: We present evidence that (i) chip-specific effects can simulate plausible differential methylation results and (ii) popular pathway analysis software developed for expression arrays can yield spurious results when used in tandem with methylation microarrays.