PMID- 23001074 OWN - NLM STAT- MEDLINE DCOM- 20130305 LR - 20220129 IS - 1528-1140 (Electronic) IS - 0003-4932 (Linking) VI - 257 IP - 2 DP - 2013 Feb TI - Murine gut microbiota and transcriptome are diet dependent. PG - 287-94 LID - 10.1097/SLA.0b013e318262a6a6 [doi] AB - 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. FAU - Carlisle, Erica M AU - Carlisle EM AD - Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA. FAU - Poroyko, Valeriy AU - Poroyko V FAU - Caplan, Michael S AU - Caplan MS FAU - Alverdy, John AU - Alverdy J FAU - Morowitz, Michael J AU - Morowitz MJ FAU - Liu, Donald AU - Liu D LA - eng GR - R21 AI099713/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann Surg JT - Annals of surgery JID - 0372354 RN - 0 (DNA, Complementary) RN - 0 (Receptors, Chemokine) SB - IM MH - Animal Feed MH - Animals MH - Animals, Newborn MH - Colon/*immunology/*microbiology MH - DNA, Complementary/genetics MH - Gene Library MH - Intestinal Mucosa/immunology MH - Metagenome/immunology MH - Mice MH - Mice, Inbred C3H MH - *Milk Substitutes MH - *Milk, Human MH - Oxidative Stress/immunology MH - Principal Component Analysis MH - Receptors, Chemokine/metabolism MH - Transcriptome EDAT- 2012/09/25 06:00 MHDA- 2013/03/06 06:00 CRDT- 2012/09/25 06:00 PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/03/06 06:00 [medline] AID - 10.1097/SLA.0b013e318262a6a6 [doi] PST - ppublish SO - Ann Surg. 2013 Feb;257(2):287-94. doi: 10.1097/SLA.0b013e318262a6a6.