The endosymbiotic role of intestinal helminths in multiple sclerosis: Promising probiotic hypothesis.

Sir,

At present, hygiene hypothesis offers the most accepted explanation for the remarkable increases of atopy and autoimmunity, which have been monitored in the developed world during the last century and which now appear to be happening in the developing world.[12] The hypothesis postulates that certain infections or other exposures may teach the immune system to not attack a person's own body as happens in an autoimmune disease such as multiple sclerosis (MS). Some experts point to the hygiene hypothesis as a possible explanation as to why MS is more prevalent in the US and Europe than in South Africa and Latin America, where people are more likely to be infected with intestinal worms and thus protected, according to the theory.[3] MS is an inflammatory disorder causing central nervous system demyelination and axonal injury; its etiology remains indefinable; however, several levels of evidence support the concept that autoimmunity plays a major role in disease pathogenesis.[3] As defined by the FAO (Food and Agriculture Organization of the United Nations), treatment protocols based on the hygiene hypothesis including the administration of live microorganisms in adequate amounts give a beneficial effects on the human health.[4] In this regard, many helminths are well adapted to their hosts and are known to reduce host inflammatory responses. In fact, all mammals, including humans, have been colonized with helminths.[5] According to the hygiene hypothesis, if microbial deprivation especially helminths causes abnormal immunoregulation and if helminths are able to promote normal immunoregulation, the logically arisen inquiry is whether helminth replacement could be beneficial in MS and related conditions.[67]

The most prominent known mechanisms of helminth-induced immunoregulation is promoting regulatory T- and B-cells; inducing a modified Th2 type immune response; inducing a tolerant phenotype in antigen-presenting cells, such as dendritic cells (DCs); producing anti-inflammatory cytokines and cytokine mimics; alternatively activated macrophages, favoring protection rather than danger signals within the innate immune system[89] A recent study finds out a key role for helminths in downregulating the pro-inflammatory Th1 cytokines, interleukin (IL)-12, interferon-gamma, and tumor necrosis factor-alpha while promoting the production of regulatory Th2 cytokines such as IL-10, IL-4, IL-5, and IL-13.[10] Based on the hygiene hypothesis, the prevalence of autoimmune and allergic disorders increased in developed countries, and it is believed that our cleaner living reduces exposure to certain microorganisms and leads to deviated and/or reduced regulation of the immune system. In addition, some evidence revealed that MS is increasing among people, particularly adolescent subjects who had high level of sanitation and minor exposure to outdoor and environmental microorganisms. Moreover, several epidemiological investigations revealed that MS prevalence correlated with childhood environments characterized by high levels of sanitation.[3] However, improved living conditions and reduced exposure to childhood infections, in particular, have been suggested as contributing to increases in atopy and autoimmunity.

In support of this health hygiene hypothesis, a number of epidemiological studies and animal models have characterized the protective immune responses induced by helminths during autoimmune and neuroinflammatory disorders, including MS.[3]

Intestinal worm-induced immunoregulatory mechanisms have been shown to work via induction of CD4+ regulatory T-cells, CD25+ regulatory cells, and regulatory B-cells and the modulation of a wide range of innate cell types including macrophages and DCs.

Significant interest has arisen in defining and characterizing specific helminth molecules with important immunomodulatory capacities as targets for therapeutic applications in the treatment or prophylaxis of autoimmune diseases. Thus, it would be critical to focus on the investigation of immunomodulatory helminth-derived molecules to selectively induce regulatory immune responses and avoid possible side effects of natural worm infections. Efforts should be focused on the production of antigen-specific immunoregulation to avoid possible interference with essential responses to other antigens.[4] Helminths produce many molecules that are homologous to mammalian cytokines. In conclusion, according to the aforementioned mechanisms and some documented evidence, we concluded the promising effective responsibility of immunogenic antigenic materials of helminths as an endosymbiotic role throughout human life. Moreover, in our opinion, these act as a favorite probiotic within other microorganisms against MS in the wormy world next to future.

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Conflicts of interest

There are no conflicts of interest.