***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Diet is an important factor in colorectal carcinogenesis ; thus , dietary supplements may have a role in colorectal cancer prevention . OBJECTIVE The objective was to establish the relative luminal , epithelial , and epigenetic consequences of prebiotic , probiotic , and synbiotic dietary supplementation in humans . DESIGN This was a r and omized , double-blind , placebo-controlled , 4-wk crossover trial of resistant starch and Bifidobacterium lactis , either alone or as a combined synbiotic preparation , in 20 human volunteers . Rectal biopsy , feces , and serum sample s were collected . The rectal mucosal endpoints were DNA methylation at 16 CpG isl and loci and LINE-1 , epithelial proliferation ( Ki67 immunohistochemistry ) , and crypt cellularity . The fecal endpoints were short-chain fatty acid concentrations , pH , ammonia , and microbiological profiles ( by denaturing gradient gel electrophoresis and sequencing ) . Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein . RESULTS Seventeen subjects completed the entire study . The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic ( P = 0.032 ) or the probiotic ( P = 0.001 ) intervention alone , in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp . These changes developed in the absence of any significant differences in fecal chemistry . There were no differences in epithelial kinetics . CONCLUSIONS This synbiotic supplementation with B. lactis and resistant starch , in the doses used , induced unique changes in fecal microflora but did not significantly alter any other fecal , serum , or epithelial variables . This trial was registered in the Australian New Zeal and Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538 Background : Hyperactive Wnt signaling is frequently observed in colorectal cancer . Higher intakes of dietary fiber [ nondigestible carbohydrates ( NDCs ) ] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway . Objectives : We investigated the effects of supplementing healthy individuals with 2 NDCs [ resistant starch ( RS ) and polydextrose ] on fecal calprotectin concentrations and Wnt pathway – related gene expression . In addition , we determined whether effects on secreted frizzled-related protein 1 ( SFRP1 ) expression are mediated via the epigenetic mechanisms DNA methylation and microRNA expression . Design : In a r and omized , double-blind , placebo-controlled trial ( the Dietary Intervention , Stem cells and Colorectal Cancer ( DISC ) Study ) , 75 healthy participants were supplemented with RS and /or polydextrose or placebo for 50 d in a 2 × 2 factorial design . Pre- and postintervention stool sample s and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes , respectively . The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction , and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing . Results : NDC supplementation did not affect fecal calprotectin concentration . SFRP1 mRNA expression was reduced by both RS ( P = 0.005 ) and polydextrose ( P = 0.053 ) . RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1 . There were no significant interactions between RS and polydextrose . Conclusions : RS and polydextrose supplementation did not affect fecal calprotectin concentrations . Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity . However , effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated . The DISC Study was registered at clinical trials.gov as NCT01214681 A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases . There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate . We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine . We also investigated if these effects were modified by MTHFR C677 T genotype . Two hundred sixteen participants out of 818 subjects who had participated in a r and omized double-blind placebo-controlled trial were selected , pre-stratified on MTHFR C677 T genotype and matched on age and smoking status . They were allocated to receive either folic acid ( 0.8 mg/d ; n = 105 ) or placebo treatment ( n = 111 ) for three years . Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed . Global DNA methylation was measured using liquid chromatography-t and em mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine . There was no difference in global DNA methylation between those r and omized to folic acid and those in the placebo group ( difference = 0.008 , 95%CI = −0.05,0.07 , P = 0.79 ) . There was also no difference between treatment groups when we stratified for MTHFR C677 T genotype ( CC , n = 76 ; CT , n = 70 ; TT , n = 70 ) , baseline erythrocyte folate status or baseline DNA methylation levels . In moderately hyperhomocysteinemic men and women , long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes . Clinical Trials.gov Background and aims : A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia . The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a r and omised , double blind , placebo controlled , parallel design . Methods : Subjects were r and omised to receive either 400 μg/day folic acid supplement ( n = 15 ) or placebo ( n = 16 ) for 10 weeks . Genomic DNA methylation , serum and erythrocyte folate , and plasma homocysteine concentrations were measured at baseline and post intervention . Results : Folic acid supplementation  increased serum and erythrocyte folate concentrations by 81 % ( 95 % confidence interval ( CI ) 57–104 % ; p<0.001 v placebo ) and 57 % ( 95 % CI 40–74 % ; p<0.001 v placebo ) , respectively , and decreased plasma homocysteine concentration by 12 % ( 95 % CI 4–20 % ; p = 0.01 v placebo ) . Folic acid supplementation result ed in increases in DNA methylation of 31 % ( 95 % CI 16–47 % ; p = 0.05 v placebo ) in leucocytes and 25 % ( 95 % CI 11–39 % ; p = 0.09 v placebo ) in colonic mucosa . Conclusions : These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid Purpose : This study evaluated the effects of black raspberries ( BRBs ) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes , cell proliferation , apoptosis , angiogenesis , and expression of Wnt pathway genes . Experimental Design : Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder ( 60 g/d ) for 1–9 weeks .  Methylation status of promoter regions of five tumor suppressor genes was quantified . Protein expression of DNA methyltransferase 1 ( DNMT1 ) and genes associated with cell proliferation , apoptosis , angiogenesis , and Wnt signaling were measured . Results : The methylation of three Wnt inhibitors , SFRP2 , SFRP5 , and WIF1 , upstream genes in Wnt pathway , and PAX6a , a developmental regulator , was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks , but not in all 20 patients with 1–9 weeks of BRB treatment . This was associated with decreased expression of DNMT1 . BRBs modulated expression of genes associated with Wnt pathway , proliferation , apoptosis , and angiogenesis in a protective direction . Conclusions : These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum . While demethylation of genes did not occur in colorectal tissues from all treated patients , the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted . Clin Cancer Res ; 17(3 ) ; 598–610 . © 2010 AACR Background / Aims : Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon . We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 ( ESR1 ) and mutL homolog 1 ( MLH1 ) genes in colonic mucosa of subjects with colorectal adenoma . Methods : This was a r and omised , double-blind , placebo-controlled trial . Subjects received either 400 µg/day folic acid ( n = 15 ) or placebo  ( n = 14 ) for 10 weeks . Blood and colonic tissue sample s were collected at baseline and after intervention to determine biomarkers of folate and vitamin B12 status , MTHFR C677 T and MS A2756 G genotypes , and ESR1 and MLH1 methylation . Results : Although serum and red cell folate increased ( p < 0.001 vs. placebo ) and plasma homocysteine decreased ( p = 0018 vs. placebo ) in the folic acid group , there were no significant changes in ESR1 ( p = 0.649 vs. placebo ) or MLH1 ( p = 0.211 vs. placebo ) methylation . There was a significant effect of gender on ESR1 methylation ( p = 0.004 ) and significant gender and genotype ( MTHFR C677 T and MS A2756 G ) interactions ( p = 0.04 and p = 0.014 , respectively ) that were independent of treatment group allocation . Conclusions : Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma . Further studies to investigate the interactions between gender , genotype and DNA methylation suggested in this study are warranted BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate 
    Output:
    
In summary , there is limited evidence from intervention studies of effects of dietary factors , other than folic acid , on DNA methylation patterns in humans .