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

Bre Riba, Kasra Hassani, Alesia Walker, Niels van Best, Dunja von Zeschwitz, Teresa Anslinger, Nina Sillner, Stefanie Rosenhain, Daniel Eibach, Oumou Maiga-Ascofare, Ulrike Rolle-Kampczyk, Marijana Basic, Anne Binz, Sabine Mocek, Beate Sodeik, Rudolf Bauerfeind, Antje Mohs, Christian Trautwein, Fabian Kiessling, Juergen MayMartin Klingenspor, Felix Gremse, Philippe Schmitt-Kopplin, Andre Bleich, Natalia Torow, Martin von Bergen, Mathias W. Hornef*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number7019
Number of pages15
JournalScience Translational Medicine
Volume12
Issue number565
DOIs
Publication statusPublished - 14 Oct 2020

Keywords

  • DEVELOPING-COUNTRIES
  • DIARRHEAL DISEASE
  • LIPID-METABOLISM
  • LAMBLIA
  • DUODENALIS
  • ACID
  • CHILDREN
  • RESPONSES
  • INFANTS
  • IMPACT

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