title: Effect of Dietary Fibers on Cecal Microbiota and Intestinal Tumorigenesis in Azoxymethane Treated A/J Min/+ Mice.
abstract: Foods naturally high in dietary fiber are generally considered to protect against development of colorectal cancer (CRC). However, the intrinsic effect of dietary fiber on intestinal carcinogenesis is unclear. We used azoxymethane (AOM) treated A/J Min/+ mice, which developed a significantly higher tumor load in the colon than in the small intestine, to compare the effects of dietary inulin (IN), cellulose (CE) or brewers spent grain (BSG) on intestinal tumorigenesis and cecal microbiota. Each fiber was tested at two dose levels, 5% and 15% (w/w) content of the AIN-93M diet. The microbiota was investigated by next-generation sequencing of the 16S rRNA gene (V4). We found that mice fed IN had approximately 50% lower colonic tumor load than mice fed CE or BSG (p<0.001). Surprisingly, all three types of fiber caused a dose dependent increase of colonic tumor load (p<0.001). The small intestinal tumor load was not affected by the dietary fiber interventions. Mice fed IN had a lower bacterial diversity than mice fed CE or BSG. The Bacteroidetes/Firmicutes ratio was significantly (p = 0.003) different between the three fiber diets with a higher mean value in IN fed mice compared with BSG and CE. We also found a relation between microbiota and the colonic tumor load, where many of the operational taxonomic units (OTUs) related to low tumor load were significantly enriched in mice fed IN. Among the OTUs related to low tumor load were bacteria affiliated with the Bacteroides genus. These results suggest that type of dietary fiber may play a role in the development of CRC, and that the suppressive effect of IN on colonic tumorigenesis is associated with profound changes in the cecal microbiota profile.
authors.affiliation: Nofima - Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Moen
authors.affiliation: Department of Pharmacology, Oslo University and Oslo University Hospital, Oslo, Norway.|Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Kristi
authors.initials: K
authors.lastname: Henjum
authors.affiliation: Nofima - Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Måge
authors.affiliation: Nofima - Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
authors.forename: Svein Halvor
authors.initials: SH
authors.lastname: Knutsen
authors.affiliation: Nofima - Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
authors.forename: Ida
authors.initials: I
authors.lastname: Rud
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Ragna Bogen
authors.initials: RB
authors.lastname: Hetland
authors.affiliation: Norwegian University of Life Sciences, Department of Food Safety and Infection Biology, Oslo Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Paulsen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001397:Azoxymethane; D041963:Bacteroidetes; D001835:Body Weight; D063646:Carcinogenesis / Q000473:pathology*; D002432:Cecum / Q000187:drug effects* / Q000382:microbiology*; D002482:Cellulose / Q000737:chemistry; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D004032:Diet; D004043:Dietary Fiber; D000068536:Bacillota; D059014:High-Throughput Nucleotide Sequencing; D007444:Inulin / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D012336:RNA, Ribosomal, 16S / Q000378:metabolism
chemical_list: D004043:Dietary Fiber; D012336:RNA, Ribosomal, 16S; D002482:Cellulose; D007444:Inulin; D001397:Azoxymethane