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Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition. Sci Transl Med 2016 Nov 23;8(366):366ra164

Date

11/25/2016

Pubmed ID

27881825

Pubmed Central ID

PMC5152673

DOI

10.1126/scitranslmed.aah4669

Scopus ID

2-s2.0-84997787497 (requires institutional sign-in at Scopus site)   43 Citations

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.

Author List

Wagner VE, Dey N, Guruge J, Hsiao A, Ahern PP, Semenkovich NP, Blanton LV, Cheng J, Griffin N, Stappenbeck TS, Ilkayeva O, Newgard CB, Petri W, Haque R, Ahmed T, Gordon JI

Author

Nicholas Semenkovich MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bacteroides fragilis
Bangladesh
Cachexia
Child Nutrition Disorders
Child, Preschool
Diet
Disease Models, Animal
Feces
Female
Gastrointestinal Microbiome
Gene Expression Regulation, Bacterial
Germ-Free Life
Humans
Infant
Male
Mice
Phenotype