Giardia antagonizes beneficial functions of indigenous and therapeutic intestinal bacteria during protein deficiency
Aadra P. Bhatt,
Jason W. Arnold,
Muyiwa Awoniyi,
Shan Sun,
Verônica Feijoli Santiago,
Deniz Coskuner,
Pedro Henrique Quintela,
Kenneth Walsh,
Jamie Xiao,
Renay Ngobeni-Nyambi,
Brenna Hansen,
Ajay S. Gulati,
Ian M. Carroll,
M. Andrea Azcarate-Peril,
Anthony A. Fodor,
Jonathan Swann,
Luther A. Bartelt
Affiliations
Aadra P. Bhatt
Division of Gastroenterology and Hepatology, Department of Medicine, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Jason W. Arnold
Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, North Carolina, USA
Muyiwa Awoniyi
Department of Gastroenterology Hepatology and Nutrition, Digestive Diseases and Surgery Institute of the Cleveland Clinic Foundation, and Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
Shan Sun
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA
Verônica Feijoli Santiago
School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
Deniz Coskuner
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Pedro Henrique Quintela
Institute of Biomedicine, Federal University of Ceará, Fortaleza, CE, Brazil
Kenneth Walsh
Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Jamie Xiao
Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Renay Ngobeni-Nyambi
Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa
Brenna Hansen
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ajay S. Gulati
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ian M. Carroll
Department of Nutrition, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
M. Andrea Azcarate-Peril
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Anthony A. Fodor
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA
Jonathan Swann
School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
Luther A. Bartelt
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp. and an increase in Bifidobacterium spp. This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp. mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia, despite not inhibiting Lactobacillus colonization. These results highlight Giardia’s potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.
