Project description:Folic acid deficiency is common worldwide and is linked to intestinal flora imbalance. The intestinal microbial utilization of folic acid based on model animals faces the challenges of repeatability and individual variability. In this study, we built an in vitro fecal slurry culture model deficient in folic acid. We examined the effects of supplementation with different forms of folic acid (5-methyltetrahydrofolate and non-reduced folic acid) on the modulation of intestinal flora. 16S rDNA gene sequencing showed alpha diversity increased after folic acid supplementation compared to fermentation samples with folic acid deficiency. In the non-reduced folic acid (FA) group, the relative abundance of the Firmicutes phylum dropped to 56.7%, whereas in the 5-methyltetrahydrofolate (MTHF) supplementation group, it grew to 64.9%. Lactobacillus genera became more prevalent, reaching 22.8% and 30.8%, respectively. Additionally, Bifidobacterium and Pedioccus, two common probiotic bacteria, were in higher abundance. Short-chain fatty acids (SCFAs) analysis showed that supplementation with folic acid (non-reduced folic acid, 5-methyltetrahydrofolate) decreased acetic acid and increased the fermentation yield of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a human folic acid deficiency model for studying intestinal microbiota and demonstrated that both 5-methyltetrahydrofolate and non-reduced folic acid have effects on the regulation of intestinal microecology.
Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.
Project description:We determined the effects of excess folic acid supplementation (5x recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of gestational dibetes (GDM; 45% kcal fat diet) and control mice (10% kcal diet) we show that folic acid supplementation increased weight gain and fat mass in both GDM and control mice but improved insulin sensitivity in GDM mice and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation may not be due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (GDM and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the offspring from supplemented dams but this differed between GDM and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype, and has sex-specific effects on offspring pancreas and liver.
Project description:Folic acid supplements prior to and during gestation are recommended and necessary to prevent neural tube defects in developing embryos. But there are also studies suggesting possible adverse effects of high-dose folic acid supplementation. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects gene expression in the offspring generation.
Project description:Folic acid is involved in DNA methylation, thereby it can potentially induce gene silencing. We used microarrays to detect the transcripts that are showing different expressions after short-term folic acid (FA) treatment.
Project description:DNA methylation profiles from saliva collected from 89 mothers and 179 adolescent children who received or did not receive perinatal folic acid supplementation Periconceptional folic acid supplementation and DNA methylation patterns in adolescents
Project description:We report that fortified levels of folic acid adversely affect cilia strucure and function. This data set agrees with previous experiements which have demonstrated that elevated folic acid levels can increase transcription variability on a genome-wide level. Furthermore, we demonstrate that among these dysregulated genes, genes contained within SYSgold cilia database are proportionally over-represented. This over-representation of cilia genes among dysregulated genes may play a key role in ciliopathys' sensitivity to elevated folic acid levels.
Project description:Increased consumption of folic acid is prevalent due to its beneficial effects to help protecting from genome damage. Growing evidence is emphasizing the side effects pointing to excessive dietary intake. Effects of paternal folic acid excessive consumption on the offspring and its transgenerational inheritance mechanism remain elusive. We hypothesize that the folic acid excessive consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation, and heritably influence offspring metabolic homeostasis. This is the results of mRNA sequencing part
Project description:Folic acid supplementation (8 mg/kg diet) promotes colon tumor formation in mice with established colitis induced by carcinogen azoxymethane (AOM) and dextran sulfate sodium sulfate (DSS). This induction of colon tumors was associated with hypomethylation of DNA cased by folic acid supplementation.