title: Changes in intestinal immunity, gut microbiota, and expression of energy metabolism-related genes explain adenoma growth in bilberry and cloudberry-fed ApcMinmice.
abstract: We showed previously that ellagitannin-rich cloudberries and anthocyanin-rich bilberries reduce the number of intestinal adenomas in multiple intestinal neoplasia/+ (ApcMin) mice. We also found that cloudberries decreased the size of adenomas, whereas bilberries increased it. Here we hypothesized that the difference in adenoma growth could be explained by dissimilar effects of the berries on intestinal immune responses and gut microbiota, potentially driven by the distinct polyphenol compositions of the 2 berries. Our objectives were to investigate lymphocyte subtypes and the predominant cecal bacterial diversity in mice fed with bilberries and cloudberries, and to analyze global gene expression profiles in the intestinal mucosa. Immunostainings of CD3+T lymphocytes, FoxP3+regulatory T lymphocytes, and CD45R+B lymphocytes revealed a smaller ratio of intraepithelial to all mucosal CD3+T lymphocytes in the cloudberry-fed mice compared with controls, suggesting an attenuation of inflammation. Bilberry feeding induced no changes in the density of any of the lymphocyte subtypes. The predominant bacterial diversity in cecal contents, analyzed using polymerase chain reaction-denaturating gradient gel electrophoresis, was higher in the bilberry group than in the control or cloudberry groups. The microbial profiles of cloudberry-fed mice clustered together and were associated with small adenoma size. Pathway analyses of gene expression data showed that cloudberry down-regulated and bilberry up-regulated the expression of energy metabolism-related genes in the intestinal mucosa. In conclusion, attenuation of intestinal inflammation, changes in microbial profiles, and down-regulation of mucosal energy metabolism may account for the smaller adenoma size in cloudberry-fed mice in comparison to bilberry-fed mice.
authors.affiliation: Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland. Electronic address: essi.paivarinta@helsinki.fi.
authors.forename: Essi
authors.initials: E
authors.lastname: Päivärinta
authors.affiliation: Division of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland. Electronic address: mikael.niku@helsinki.fi.
authors.forename: Mikael
authors.initials: M
authors.lastname: Niku
authors.affiliation: VTT Technical Research Centre of Finland Ltd, PO Box 1000, FIN-02044 VTT, Espoo, Finland. Electronic address: johanna.maukonen@vtt.fi.
authors.forename: Johanna
authors.initials: J
authors.lastname: Maukonen
authors.affiliation: School of Pharmacy, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland. Electronic address: markus.storvik@uef.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
authors.affiliation: Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland. Electronic address: anu.heiman-lindh@helsinki.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Heiman-Lindh
authors.affiliation: VTT Technical Research Centre of Finland Ltd, PO Box 1000, FIN-02044 VTT, Espoo, Finland. Electronic address: maria.saarela@vtt.fi.
authors.forename: Maria
authors.initials: M
authors.lastname: Saarela
authors.affiliation: Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland. Electronic address: anne-maria.pajari@helsinki.fi.
authors.forename: Anne-Maria
authors.initials: AM
authors.lastname: Pajari
authors.affiliation: Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, PO Box 66, Helsinki FIN-00014, Finland. Electronic address: marja.mutanen@helsinki.fi.
authors.forename: Marja
authors.initials: M
authors.lastname: Mutanen
mesh_terms: D000818:Animals; D004269:DNA, Bacterial / Q000235:genetics; D004032:Diet; D004195:Disease Models, Animal; D015536:Down-Regulation; D004734:Energy Metabolism; D005260:Female; D005638:Fruit / Q000737:chemistry; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007414:Intestinal Neoplasms / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D029800:Vaccinium myrtillus / Q000737:chemistry
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S
keywords: Adenomatous; Gene expression; Mice; Microbiota; Polyphenols; Polyposis coli; Regulatory T lymphocytes