title: Murine gut microbiota and transcriptome are diet dependent.
abstract: OBJECTIVE
  Here, we determine how formula feeding impacts the gut microbiota and host transcriptome.
  
  
  BACKGROUND
  Formula-fed (FF) infants are at risk for diseases that involve complex interactions between microbes and host immune elements such as necrotizing enterocolitis. The aims of this study were to simultaneously examine the microbiota and host transcriptional profiles of FF and maternal-fed (MF) mice to evaluate how diet impacts gut colonization and host genes.
  
  
  METHODS
  After 72 hours of FF or MF, colonic tissue was collected. 16S ribosomal RNA was sequenced with Roche GS-FLX (Genome Sequencer-FLX) pyrosequencing. Operational taxonomical unit clustering, diversity analysis, and principal coordinate analysis (PCA) were performed. Complementary DNA libraries were sequenced by Solexa. Reads were annotated by BLAST (Basic Local Alignment Search Tool) search against mouse RNA database [National Center for Biotechnology Information (NCBI) build-37] and functionally classified using the KOG (Eukaryotic Orthologous Groups) database (NCBI).
  
  
  RESULTS
  Firmicutes (P < 0.001) was the dominant phylum in MF pups, whereas Proteobacteria (P < 0.001) and Bacteroidetes (P < 0.05) were dominant in FF mice. On the genus level, FF mice had increased Serratia (P < 0.001) and Lactococcus (P < 0.05) whereas MF mice had increased Lactobacillus (P < 0.001). PCA confirmed clustering by diet. Solexa sequencing demonstrated different (P < 0.05) messenger RNA transcript levels in 148 genes. Heme oxygenase 1 (P < 0.01), an oxidative stress marker, was increased 25-fold in FF mice. In addition, decreased vinculin (P < 0.05), a cytoskeletal protein associated with adherens junctions in FF pups suggested impaired gut structural integrity. Diet also impacted immune regulation, cell cycle control/gene expression, cell motility, and vascular function genes.
  
  
  CONCLUSIONS
  FF shifted gut microbiota and structural integrity, oxidative stress, and immune function genes, presumably increasing vulnerability to disease in FF mice. Interrogation of microbial and host gene expression in FF neonates may offer new insight on how diet affects disease pathogenesis.
authors.affiliation: Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Carlisle
authors.forename: Valeriy
authors.initials: V
authors.lastname: Poroyko
authors.forename: Michael S
authors.initials: MS
authors.lastname: Caplan
authors.forename: John
authors.initials: J
authors.lastname: Alverdy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morowitz
authors.forename: Donald
authors.initials: D
authors.lastname: Liu
mesh_terms: D000821:Animal Feed; D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000276:immunology* / Q000382:microbiology*; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D007413:Intestinal Mucosa / Q000276:immunology; D054892:Metagenome / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D041941:Milk Substitutes; D008895:Milk, Human; D018384:Oxidative Stress / Q000276:immunology; D025341:Principal Component Analysis; D019707:Receptors, Chemokine / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018076:DNA, Complementary; D019707:Receptors, Chemokine