title: Changes in composition of caecal microbiota associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.
abstract: Human inflammatory bowel disease (IBD) is a chronic intestinal disease where the resident microbiota contributes to disease development, yet the specific mechanisms remain unclear. Interleukin-10 gene-deficient (Il10-/-) mice develop inflammation similar to IBD, due in part to an inappropriate response to commensal bacteria. We have previously reported changes in intestinal morphology and colonic gene expression in Il10-/- mice in response to oral bacterial inoculation. In this study, we aimed to identify specific changes in the caecal microbiota associated with colonic inflammation in these mice. The microbiota was evaluated using pyrotag sequencing, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR. Microbiota profiles were influenced by genotype of the mice and by bacterial inoculation, and a strong correlation was observed between the microbiota and colonic inflammation scores. Although un-inoculated Il10-/- and C57 mice had similar microbiota communities, bacterial inoculation resulted in different changes to the microbiota in Il10-/- and C57 mice. Inoculated Il10-/- mice had significantly less total bacteria than un-inoculated Il10-/- mice, with a strong negative correlation between total bacterial numbers, relative abundance of Escherichia/Shigella, microbiota diversity, and colonic inflammation score. Our results show a putative causative role for the microbiota in the development of IBD, with potentially key roles for Akkermansia, or for Bacteroides, Helicobacter, Parabacteroides, and Alistipes, depending on the composition of the bacterial inoculum. These data support the use of bacterially-inoculated Il10-/- mice as an appropriate model to investigate human IBD.
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North 4442, New Zealand. warren.mcnabb@agresearch.co.nz.|Nutrigenomics New Zealand, Private Bag 92019, Auckland 1142, New Zealand. warren.mcnabb@agresearch.co.nz.
authors.forename: Shalome A
authors.initials: SA
authors.lastname: Bassett
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North 4442, New Zealand. warren.mcnabb@agresearch.co.nz.|Nutrigenomics New Zealand, Private Bag 92019, Auckland 1142, New Zealand. warren.mcnabb@agresearch.co.nz.
authors.forename: Wayne
authors.initials: W
authors.lastname: Young
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North 4442, New Zealand. matthew.barnett@agresearch.co.nz.|Nutrigenomics New Zealand, Private Bag 92019, Auckland 1142, New Zealand. matthew.barnett@agresearch.co.nz.|Gravida: National Centre for Growth and Development, Private Bag 92019, Auckland 1142, New Zealand. matthew.barnett@agresearch.co.nz.
authors.forename: Matthew P G
authors.initials: MP
authors.lastname: Barnett
authors.affiliation: Food Assurance & Meat Quality Team, Food & Bio-based Products Group, AgResearch Grasslands, Tennent Drive, Palmerston North 4442, New Zealand. adrian.cookson@agresearch.co.nz.|Riddet Institute, Massey University, Tennent Drive, Palmerston North 4474, New Zealand. adrian.cookson@agresearch.co.nz.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Cookson
authors.affiliation: Nutrigenomics New Zealand, Private Bag 92019, Auckland 1142, New Zealand. warren.mcnabb@agresearch.co.nz.|Riddet Institute, Massey University, Tennent Drive, Palmerston North 4474, New Zealand. warren.mcnabb@agresearch.co.nz.|AgResearch Grasslands, Tennent Drive, Palmerston North 4442, New Zealand. warren.mcnabb@agresearch.co.nz.
authors.forename: Warren C
authors.initials: WC
authors.lastname: McNabb
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North 4442, New Zealand. warren.mcnabb@agresearch.co.nz.|Nutrigenomics New Zealand, Private Bag 92019, Auckland 1142, New Zealand. warren.mcnabb@agresearch.co.nz.|Gravida: National Centre for Growth and Development, Private Bag 92019, Auckland 1142, New Zealand. warren.mcnabb@agresearch.co.nz.|Riddet Institute, Massey University, Tennent Drive, Palmerston North 4474, New Zealand. warren.mcnabb@agresearch.co.nz.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Roy
mesh_terms: D000818:Animals; D001419:Bacteria; D044822:Biodiversity; D002432:Cecum / Q000382:microbiology*; D003092:Colitis / Q000382:microbiology*; D016983:Enterococcus; D005838:Genotype; D007249:Inflammation / Q000382:microbiology*; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota
chemical_list: D016753:Interleukin-10