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Murine Gut Microbiota and Transcriptome Are Diet Dependent

Carlisle, Erica M. MD*; Poroyko, Valeriy PhD*; Caplan, Michael S. MD; Alverdy, John MD*; Morowitz, Michael J. MD; Liu, Donald MD, PhD*

doi: 10.1097/SLA.0b013e318262a6a6
Original Articles

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.

Supplemental Digital Content is available in the text.Formula-fed infants are at risk for diseases that involve complex interactions between microbes and host immune elements such as necrotizing enterocolitis. Here, we use culture-independent techniques to show that formula fed shifts gut microbiota and alters structural integrity, oxidative stress, and immune gene expression, presumably increasing vulnerability to disease.

*Department of Surgery, The University of Chicago Medical Center, Chicago, IL

Department of Pediatrics, Northshore University HealthSystem, Evanston, IL

Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Reprints: Donald Liu, MD, PhD, Department of Surgery, The University of Chicago Medical Center, 5839 S Maryland Avenue, Chicago, IL 60637. E-mail:

Disclosure: This work has been supported by an internal grant from the University of Chicago. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

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© 2013 Lippincott Williams & Wilkins, Inc.