title: Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications.
abstract: BACKGROUND
  The Hygiene Hypothesis (HH) attributes the dramatic increase in autoimmune and allergic diseases observed in recent decades in Western countries to the reduced exposure to diverse immunoregulatory infectious agents. This theory has since largely been supported by strong epidemiological and experimental evidence.
  
  
  CONCLUSIONS
  The analysis of these data along with the evolution of the Western world's microbiome enable us to obtain greater insight into microorganisms involved in the HH, as well as their regulatory mechanisms on the immune system. Helminthes and their derivatives were shown to have a protective role. Helminthes' broad immunomodulatory properties have already begun to be exploited in clinical trials of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and type-1 diabetes.
  
  
  CONCLUSIONS
  In this review, we will dissect the microbial actors thought to be involved in the HH as well as their immunomodulatory mechanisms as emphasized by experimental studies, with a particular attention on parasites. Thereafter, we will review the early clinical trials using helminthes' derivatives focusing on autoimmune diseases.
authors: The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. mathildemarie.v@gmail.com.|Department of Internal Medicine, Archet-1 Hospital, University of Nice-Sophia-Antipolis, 151 Route de Saint Antoine de Ginestière, 06202, Nice, France. mathildemarie.v@gmail.com.
authors: Mathilde
authors: M
authors: Versini
authors: Department of Internal Medicine, Archet-1 Hospital, University of Nice-Sophia-Antipolis, 151 Route de Saint Antoine de Ginestière, 06202, Nice, France. jeandel.py@chu-nice.fr.
authors: Pierre-Yves
authors: PY
authors: Jeandel
authors: The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. tomerbashi@gmail.com.
authors: Tomer
authors: T
authors: Bashi
authors: The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. giorgia.bizzaro@gmail.com.
authors: Giorgia
authors: G
authors: Bizzaro
authors: The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. jeandel.py@chu-nice.fr.
authors: Miri
authors: M
authors: Blank
authors: The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. shoenfel@post.tau.ac.il.|The Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. shoenfel@post.tau.ac.il.
authors: Yehuda
authors: Y
authors: Shoenfeld
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D006373:Helminthiasis / Q000276:immunology; D006801:Humans; D061148:Hygiene Hypothesis
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth