Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy

Natasa Giallourou (), Jason Arnold, Elizabeth T. Rogawski McQuade, Muyiwa Awoniyi, Rose Viguna Thomas Becket, Kenneth Walsh, Jeremy Herzog, Ajay S. Gulati, Ian M. Carroll, Stephanie Montgomery, Pedro Henrique Quintela, Angela M. Faust, Steven M. Singer, Anthony A. Fodor, Tahmeed Ahmad, Mustafa Mahfuz, Esto Mduma, Thomas Walongo, Richard L. Guerrant, R. Balfour Sartor, Jonathan R. Swann, Margaret N. Kosek and Luther A. Bartelt ()
Additional contact information
Natasa Giallourou: Imperial College London
Jason Arnold: University of North Carolina at Chapel Hill
Elizabeth T. Rogawski McQuade: Emory University
Muyiwa Awoniyi: University of North Carolina at Chapel Hill
Rose Viguna Thomas Becket: The University of North Carolina at Chapel Hill
Kenneth Walsh: The University of North Carolina at Chapel Hill
Jeremy Herzog: University of North Carolina at Chapel Hill
Ajay S. Gulati: The University of North Carolina at Chapel Hill
Ian M. Carroll: The University of North Carolina at Chapel Hill
Stephanie Montgomery: The University of North Carolina at Chapel Hill
Pedro Henrique Quintela: Federal University of Ceará
Angela M. Faust: Waterborne, Inc
Steven M. Singer: Georgetown University
Anthony A. Fodor: The University of North Carolina Charlotte, Department of Bioinformatics and Genomics
Tahmeed Ahmad: International Center for Diarrheal Disease Research
Mustafa Mahfuz: International Center for Diarrheal Disease Research
Esto Mduma: Haydom Lutheran Hospital
Thomas Walongo: Haydom Lutheran Hospital
Richard L. Guerrant: The University of Virginia Charlottesville
R. Balfour Sartor: University of North Carolina at Chapel Hill
Jonathan R. Swann: University of Southampton
Margaret N. Kosek: The University of Virginia Charlottesville
Luther A. Bartelt: University of North Carolina at Chapel Hill

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected children demonstrate broad amino acid deficiencies, and overproduction of specific phenolic acids, byproducts of intestinal bacterial amino acid metabolism. Gnotobiotic mice require specific nutritional and environmental conditions to recapitulate these findings, and immunodeficient mice confirm a pathway independent of chronic T/B cell inflammation. Taken together, we propose a new paradigm that Giardia-mediated growth faltering is contingent upon a convergence of this intestinal protozoa with nutritional and intestinal bacterial factors.

Date: 2023
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DOI: 10.1038/s41467-023-38363-2

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