Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications

Abstract

BackgroundThe 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.DiscussionThe 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.SummaryIn 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.

Revisiting the hygiene hypothesis for allergy and asthma

“…65,66 Effective translation to help address the unmet need of allergy and asthma prevention in human health has been elusive. Compelling scientific leads have been followed in randomized clinical trials without significant benefit for patients and doctors in airways allergy and asthma clinics.…”

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

“…A hygienic lifestyle can also lead to decreased exposure to indigenous viruses such as Hepatitis A, pathogenic bacteria such as Heliobacter pylori, Salmonella spp., Mycobacterium tuberculosis , and parasites like helminths and Toxoplasma gondii (19). Anecdotal evidence has shown that parasitic infection diminishes or eliminates allergic reactions (11) probably because helminths can modulate the gut microbiota and DCs toward a more tolerogenic phenotype (20). For example, Nod2 knockout (KO) mice showed that intestinal helminth infection prevented the colonization of inflammatory Bacteriodes vulgatus and promoted the colonization of protective microbiota enriched in Clostridiales, which was caused by a T helper cell type 2 immune response (21).…”

Environmental factors in autoimmune diseases and their role in multiple sclerosis

“…Infections that might confer a protective effect to the host are colonizations of the GIT by parasitic worms. Different studies have shown that helminths may affect the host’s immune response by the promotion of an anti-inflammatory environment [85, 86]. Based on this, the possibility of treating MS with helminths has already been explored in animal models [87–89] and also phase 1 clinical trials [90].…”