title: Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice.
abstract: Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mice with the fecal microbiota from healthy control individuals or IBS patients with diarrhea (IBS-D), with or without anxiety, and monitored gut function and behavior in the transplanted mice. Microbiota profiles in recipient mice clustered according to the microbiota profiles of the human donors. Mice receiving the IBS-D fecal microbiota showed a taxonomically similar microbial composition to that of mice receiving the healthy control fecal microbiota. However, IBS-D mice showed different serum metabolomic profiles. Mice receiving the IBS-D fecal microbiota, but not the healthy control fecal microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation, and anxiety-like behavior. These results indicate the potential of the gut microbiota to contribute to both intestinal and behavioral manifestations of IBS-D and suggest the potential value of microbiota-directed therapies in IBS patients.
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Giada
authors.identifier: 0000-0002-2063-7741
authors.initials: G
authors.lastname: De Palma
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Michael D J
authors.identifier: 0000-0002-9332-747X
authors.initials: MD
authors.lastname: Lynch
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Vi T
authors.initials: VT
authors.lastname: Dang
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yikang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jury
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Genevieve
authors.identifier: 0000-0001-9575-4689
authors.initials: G
authors.lastname: Umeh
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Miranda
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Marc
authors.identifier: 0000-0001-6801-3017
authors.initials: M
authors.lastname: Pigrau Pastor
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sacha
authors.identifier: 0000-0001-9669-0082
authors.initials: S
authors.lastname: Sidani
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maria Ines
authors.identifier: 0000-0002-9040-9824
authors.initials: MI
authors.lastname: Pinto-Sanchez
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Vivek
authors.initials: V
authors.lastname: Philip
authors.affiliation: Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Peter G
authors.initials: PG
authors.lastname: McLean
authors.affiliation: Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.
authors.forename: Moreno-Gabriel
authors.identifier: 0000-0002-2457-4450
authors.initials: MG
authors.lastname: Hagelsieb
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Gabriela E
authors.identifier: 0000-0002-1820-2992
authors.initials: GE
authors.lastname: Bergonzelli
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Philip
authors.identifier: 0000-0001-9296-3223
authors.initials: P
authors.lastname: Britz-McKibbin
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Josh D
authors.identifier: 0000-0002-8722-8571
authors.initials: JD
authors.lastname: Neufeld
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Collins
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. bercikp@mcmaster.ca.
authors.forename: Premysl
authors.identifier: 0000-0001-8707-1781
authors.initials: P
authors.lastname: Bercik
mesh_terms: D000328:Adult; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal; D016022:Case-Control Studies; D003106:Colon / Q000276:immunology / Q000382:microbiology; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D005772:Gastrointestinal Transit; D005856:Germ-Free Life; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000382:microbiology*; D008297:Male; D055432:Metabolomics; D051379:Mice; D014019:Tissue Donors