Research ArticleMICROBIOTA

Disturbed gut microbiota and bile homeostasis in Giardia-infected mice contributes to metabolic dysregulation and growth impairment

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Science Translational Medicine  14 Oct 2020:
Vol. 12, Issue 565, eaay7019
DOI: 10.1126/scitranslmed.aay7019

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A parasite’s bilious defense

The enteropathogenic parasite Giardia lamblia is a frequent cause of self-limited diarrhea in infected adult travelers. In contrast, parasite infection of children in endemic areas is not associated with diarrheal disease but rather with reduced growth and body weight gain. Riba et al. established a G. lamblia infection model in neonatal mice. Infected neonatal animals displayed reduced growth and weight gain. Analysis of these animals showed that G. lamblia induced bile secretion and that an altered gut microbiota composition, bile acid modification by commensal bacteria, and subsequent alterations of lipid metabolism contributed to this phenotype.

Abstract

Although infection with the human enteropathogen Giardia lamblia causes self-limited diarrhea in adults, infant populations in endemic areas experience persistent pathogen carriage in the absence of diarrhea. The persistence of this protozoan parasite in infants has been associated with reduced weight gain and linear growth (height-for-age). The mechanisms that support persistent infection and determine the different disease outcomes in the infant host are incompletely understood. Using a neonatal mouse model of persistent G. lamblia infection, we demonstrate that G. lamblia induced bile secretion and used the bile constituent phosphatidylcholine as a substrate for parasite growth. In addition, we show that G. lamblia infection altered the enteric microbiota composition, leading to enhanced bile acid deconjugation and increased expression of fibroblast growth factor 15. This resulted in elevated energy expenditure and dysregulated lipid metabolism with reduced adipose tissue, body weight gain, and growth in the infected mice. Our results indicate that this enteropathogen’s modulation of bile acid metabolism and lipid metabolism in the neonatal mouse host led to an altered body composition, suggesting how G. lamblia infection could contribute to growth restriction in infants in endemic areas.

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