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A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response

Scott Schwartz12, Iddo Friedberg39, Ivan V Ivanov45, Laurie A Davidson14, Jennifer S Goldsby4, David B Dahl2, Damir Herman6, Mei Wang7, Sharon M Donovan7 and Robert S Chapkin138*

Author Affiliations

1 Training Program in Biostatistics, Bioinformatics, Nutrition and Cancer, Texas A&M University, 155 Ireland Street, College Station, TX 77843, USA

2 Department of Statistics, Texas A&M University, 155 Ireland Street, College Station, TX 77843, USA

3 Department of Microbiology, Miami University, 700 East High St, Oxford, OH 45056, USA

4 Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX 77843, USA

5 Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA

6 Division of Hematology and Oncology, Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR 72205, USA

7 Department of Food Science and Human Nutrition, 905 S. Goodwin Avenue, University of Illinois, Urbana, IL 61801, USA

8 Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, 8441 State Hwy 47, Bryan, TX 77807, USA

9 Computer Science and Software Engineering, Miami University, 700 East High St, Oxford, OH 45056, USA

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Genome Biology 2012, 13:r32  doi:10.1186/gb-2012-13-4-r32

Published: 30 April 2012



Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly affecting the health and well-being of the host. Thus, it is important to develop a synthetic approach to study the host transcriptome and the microbiome simultaneously. Early microbial colonization in infants is critically important for directing neonatal intestinal and immune development, and is especially attractive for studying the development of human-commensal interactions. Here we report the results from a simultaneous study of the gut microbiome and host epithelial transcriptome of three-month-old exclusively breast- and formula-fed infants.


Variation in both host mRNA expression and the microbiome phylogenetic and functional profiles was observed between breast- and formula-fed infants. To examine the interdependent relationship between host epithelial cell gene expression and bacterial metagenomic-based profiles, the host transcriptome and functionally profiled microbiome data were subjected to novel multivariate statistical analyses. Gut microbiota metagenome virulence characteristics concurrently varied with immunity-related gene expression in epithelial cells between the formula-fed and the breast-fed infants.


Our data provide insight into the integrated responses of the host transcriptome and microbiome to dietary substrates in the early neonatal period. We demonstrate that differences in diet can affect, via gut colonization, host expression of genes associated with the innate immune system. Furthermore, the methodology presented in this study can be adapted to assess other host-commensal and host-pathogen interactions using genomic and transcriptomic data, providing a synthetic genomics-based picture of host-commensal relationships.