Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy.

Autor: Giallourou N; Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, London, UK. natasagiallourou@gmail.com.; Centre of Excellence in Biobanking and Biomedical Research, Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus. natasagiallourou@gmail.com., Arnold J; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC, 27710, USA., McQuade ETR; Department of Epidemiology, Emory University, Atlanta, GA, USA., Awoniyi M; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Becket RVT; Departments of Pediatrics and Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Walsh K; Institute for Infectious Diseases and Global Health and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Herzog J; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Gulati AS; Departments of Pediatrics and Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Carroll IM; Department of Nutrition, Gillings School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Montgomery S; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Quintela PH; Institute of Biomedicine, Federal University of Ceará, Fortaleza, CE, Brazil., Faust AM; Waterborne, Inc, New Orleans, LA, USA., Singer SM; Department of Biology, Georgetown University, Washington, DC, USA., Fodor AA; The University of North Carolina Charlotte, Department of Bioinformatics and Genomics, Charlotte, USA., Ahmad T; International Center for Diarrheal Disease Research, Dhaka, Bangladesh., Mahfuz M; International Center for Diarrheal Disease Research, Dhaka, Bangladesh., Mduma E; Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania., Walongo T; Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania., Guerrant RL; Division of Infectious Diseases and International Health, Department of Medicine, The University of Virginia Charlottesville, Charlottesville, VA, USA., Balfour Sartor R; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Swann JR; School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK., Kosek MN; Division of Infectious Diseases and International Health, Department of Medicine, The University of Virginia Charlottesville, Charlottesville, VA, USA., Bartelt LA; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. luther_bartelt@med.unc.edu.; Institute for Infectious Diseases and Global Health and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. luther_bartelt@med.unc.edu.; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. luther_bartelt@med.unc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 18; Vol. 14 (1), pp. 2840. Date of Electronic Publication: 2023 May 18.
DOI: 10.1038/s41467-023-38363-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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