title: Genetic and transcriptional analysis of human host response to healthy gut microbiota.
abstract: Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota in human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with diseases that have been previously linked to the microbiome, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiota. Of these 12 genes, eight have been associated with diseases linked to the gut microbiota, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiota interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiota in health and disease.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Richards
authors.affiliation: Departments of Genetics, Cell Biology, and Development, The University of Minnesota, Minneapolis, MN; Department of Ecology, Evolution, and Behavior, The University of Minnesota, Minneapolis, MN.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Burns
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI.
authors.forename: Adnan
authors.initials: A
authors.lastname: Alazizi
authors.affiliation: Department of Pediatrics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, QC, Canada.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Roger
authors.initials: R
authors.lastname: Pique-Regi
authors.affiliation: Departments of Genetics, Cell Biology, and Development, The University of Minnesota, Minneapolis, MN; Department of Ecology, Evolution, and Behavior, The University of Minnesota, Minneapolis, MN.
authors.forename: Ran
authors.initials: R
authors.lastname: Blekhman
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luca