title: Dual epithelial and immune cell function of Dvl1 regulates gut microbiota composition and intestinal homeostasis.
abstract: Homeostasis of the gastrointestinal (GI) tract is controlled by complex interactions between epithelial and immune cells and the resident microbiota. Here, we studied the role of Wnt signaling in GI homeostasis usingDisheveled 1knockout (Dvl1-/-) mice, which display an increase in whole gut transit time. This phenotype is associated with a reduction and mislocalization of Paneth cells and an increase in CD8+T cells in the lamina propria. Bone marrow chimera experiments demonstrated that GI dysfunction requires abnormalities in both epithelial and immune cells.Dvl1-/-mice exhibit a significantly distinct GI microbiota, and manipulation of the gut microbiota in mutant mice rescued the GI transit abnormality without correcting the Paneth and CD8+T cell abnormalities. Moreover, manipulation of the gut microbiota in wild-type mice induced a GI transit abnormality akin to that seen inDvl1-/-mice. Together, these data indicate that microbiota manipulation can overcome host dysfunction to correct GI transit abnormalities. Our findings illustrate a mechanism by which the epithelium and immune system coregulate gut microbiota composition to promote normal GI function.
authors.affiliation: Department of Pediatrics and Institute for Human Genetics.|Department of Orofacial Sciences and Program in Craniofacial Biology.
authors.forename: Haim
authors.initials: H
authors.lastname: Belinson
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology & Immunology, and.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Savage
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Fadrosh
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Yien-Ming
authors.initials: YM
authors.lastname: Kuo
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Din
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Valladares
authors.affiliation: Department of Pediatrics and Institute for Human Genetics.|Department of Orofacial Sciences and Program in Craniofacial Biology.
authors.forename: Ysbrand
authors.initials: Y
authors.lastname: Nusse
authors.affiliation: Department of Pediatrics and Institute for Human Genetics.|Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology & Immunology, and.|Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.affiliation: Department of Pediatrics and Institute for Human Genetics.|Department of Orofacial Sciences and Program in Craniofacial Biology.
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein