title: Dietary folate does not significantly affect the intestinal microbiome, inflammation or tumorigenesis in azoxymethane-dextran sodium sulphate-treated mice.
abstract: Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7-20 v. 0%, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13-83% increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r - 0·58, P= 0·02) and load (r - 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: MacFarlane
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Behan
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Fernando M G
authors.initials: FM
authors.lastname: Matias
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Judy
authors.initials: J
authors.lastname: Green
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Don
authors.initials: D
authors.lastname: Caldwell
authors.affiliation: Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Drive, AL 2203E, Ottawa, ON, Canada K1A 0K9.
authors.forename: Stephen P J
authors.initials: SP
authors.lastname: Brooks
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000737:chemistry; D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications / Q000382:microbiology; D003106:Colon / Q000382:microbiology; D003110:Colonic Neoplasms / Q000150:complications / Q000382:microbiology; D016264:Dextran Sulfate / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004032:Diet; D018450:Disease Progression; D005492:Folic Acid / Q000737:chemistry*; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009369:Neoplasms / Q000517:prevention & control*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013431:Sulfates / Q000737:chemistry
chemical_list: D015415:Biomarkers; D003911:Dextrans; D012336:RNA, Ribosomal, 16S; D013431:Sulfates; C012036:sodium sulfate; D016264:Dextran Sulfate; D005492:Folic Acid; D001397:Azoxymethane