title: Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.
abstract: The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Giacomin
authors.affiliation: Bioinformatics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Martha
authors.initials: M
authors.lastname: Zakrzewski
authors.affiliation: Prince Charles Hospital, Brisbane, QLD, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Croese
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Su
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Javier
authors.initials: J
authors.lastname: Sotillo
authors.affiliation: Prince Charles Hospital, Brisbane, QLD, Australia.
authors.forename: Leisa
authors.initials: L
authors.lastname: McCann
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Severine
authors.initials: S
authors.lastname: Navarro
authors.affiliation: The Genome Institute, and.|Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
authors.affiliation: Bioinformatics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.|Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cantacessi
mesh_terms: D000723:Ancylostomatoidea / Q000276:immunology; D000818:Animals; D044822:Biodiversity; D016022:Case-Control Studies; D002446:Celiac Disease / Q000209:etiology* / Q000628:therapy; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D005983:Glutens / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006725:Hookworm Infections / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D054892:Metagenome; D056186:Metagenomics / Q000379:methods
chemical_list: D005983:Glutens