title: Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition.
abstract: To model how interactions among enteropathogens and gut microbial community members contribute to undernutrition, we colonized gnotobiotic mice fed representative Bangladeshi diets with sequenced bacterial strains cultured from the fecal microbiota of two 24-month-old Bangladeshi children: one healthy and the other underweight. The undernourished donor's bacterial collection contained an enterotoxigenic Bacteroides fragilis strain (ETBF), whereas the healthy donor's bacterial collection contained two nontoxigenic strains of B. fragilis (NTBF). Analyses of mice harboring either the unmanipulated culture collections or systematically manipulated versions revealed that ETBF was causally related to weight loss in the context of its native community but not when introduced into the healthy donor's community. This phenotype was transmissible from the dams to their offspring and was associated with derangements in host energy metabolism manifested by impaired tricarboxylic acid cycle activity and decreased acyl-coenzyme A utilization. NTBF reduced ETBF's expression of its enterotoxin and mitigated the effects of ETBF on the transcriptomes of other healthy donor community members. These results illustrate how intraspecific (ETBF-NTBF) and interspecific interactions influence the effects of harboring B. fragilis.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Vitas E
authors.initials: VE
authors.lastname: Wagner
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.|Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Neelendu
authors.initials: N
authors.lastname: Dey
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Janaki
authors.initials: J
authors.lastname: Guruge
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ansel
authors.initials: A
authors.lastname: Hsiao
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Ahern
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Semenkovich
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Blanton
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Griffin
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.|Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Departments of Medicine, Microbiology, and Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: William
authors.initials: W
authors.lastname: Petri
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka 1212, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka 1212, Bangladesh.
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. jgordon@wustl.edu.|Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000302:isolation & purification; D001459:Bangladesh; D002100:Cachexia / Q000382:microbiology; D015362:Child Nutrition Disorders / Q000382:microbiology*; D002675:Child, Preschool; D004032:Diet; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D015964:Gene Expression Regulation, Bacterial; D005856:Germ-Free Life / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D010641:Phenotype