It may be helpful to break down the topic into three (maybe four?) issues when it comes to experimental hookworm (intestinal helminth) infections,
- Recognition that there are fundamental differences and gaps between natural and experimental helminth infections.
- Possible ways the body may control helminth infections in the first instance, and
- In turn, how helminth infections could influence the body’s ability to control other infections.
- What kinds of microbiota composition changes do the experimental helminth infections help engender and what are their long-term consequences?
Fundamental differences between natural and experimental helminth infections
Natural infections are the source of our knowledge about helminths and how our bodies respond to them. While experimental helminth infections have now shown promising results in a wide variety of experimental mouse models of inflammatory conditions such as allergies and autoimmunities, and while there have even been a few human clinical trials, major gap lies in the fact that none of the human studies thus far have engaged in long-term follow up.
- Are these therapies safe in the long-term?
- Are these therapies effective in the long-term?
Since these questions remain as yet unanswered, we perforce need to use natural helminth infections as the surrogate to assess long-term impact of experimental helminth infections. However, doing so also means acknowledging essential gaps between natural and experimental helminth infections.
- Some people are able to control natural helminth infections effectively, other aren’t able to do so, still others manage to not get infected even when they live in helminth endemic areas and likely have been exposed.
- If we assume all three groups to be equally likely to get infected, that obviously means the immune systems of these three groups of individuals function very differently.
- Those differences could be attributed to any number of factors – their genetic polymorphisms, differences in their epigenetics, microbiota, nutrition status, co-morbidities, to name just a few obvious determining factors.
- Clearly, there are major gaps in our understanding of how natural helminth infections play out in endemic regions.
- People who submit to experimental helminth infections would obviously do so in order to alleviate some underlying inflammatory disease, be it an allergy or autoimmunity.
- How would their underlying condition influence how they respond to the helminth?
- Which natural infection outcome acts as a reasonable surrogate for them?
- Clearly, there are major gaps in how to apply knowledge of natural helminth infections to their experimental counterparts.
How the body might control (experimental) intestinal helminth infections
A “light” hookworm infection is very much a matter of interpretation. So much depends on the prevailing health of that body, the health of the immune system of that body and how it responds to this infection.
Helminthologists typically classify response to helminths as either asymptomatic but carrying a relatively high parasite burden or the converse, showing signs of chronic immunopathology but with a lower parasite burden (below from).
At this point, so little is definitively known, it’s a coin toss whether the outcome of an experimental “light” helminth infection would be tolerance or debilitating pathology.
How (experimental) intestinal helminth infections could influence the body’s ability to control other infections
Epidemiological studies suggest natural hookworm infections could impede immune responses against TB, a bacterial pathogen, in TB-infected patients, malaria, a parasite, in malaria-infected patients and HIV, a virus, in HIV-infected patients, leaving open the question whether experimental helminth therapy could render a person more vulnerable to such diseases (below from 2).
Plenty of data reported thus far that experimental intestinal helminth infections modify gut microbiota composition (, 4, , , , , 9). Not much known as yet about the long-term consequences of such changes.
1. McSorley, Henry J., and Rick M. Maizels. “Helminth infections and host immune regulation.” Clinical microbiology reviews 25.4 (2012): 585-608.
2. Salgame, Padmini, George S. Yap, and William C. Gause. “Effect of helminth-induced immunity on infections with microbial pathogens.” Nature immunology 14.11 (2013): 1118.
3. Giacomin, Paul, et al. “Suppression of inflammation by helminths: a role for the gut microbiota?.” Philosophical Transactions of the Royal Society B: Biological Sciences 370.1675 (2015): 20140296.
4. Mutapi, Francisca. “The gut microbiome in the helminth infected host.” Trends in parasitology 31.9 (2015): 405-406.
5. Reynolds, Lisa A., B. Brett Finlay, and Rick M. Maizels. “Cohabitation in the intestine: interactions among helminth parasites, bacterial microbiota, and host immunity.” The Journal of Immunology 195.9 (2015): 4059-4066.
6. Giacomin, Paul, Zainab Agha, and Alex Loukas. “Helminths and intestinal flora team up to improve gut health.” Trends in parasitology 32.9 (2016): 664-666.
7. Zaiss, M. M., and N. L. Harris. “Interactions between the intestinal microbiome and helminth parasites.” Parasite immunology 38.1 (2016): 5-11.
8. Brosschot, Tara P., and Lisa A. Reynolds. “The impact of a helminth-modified microbiome on host immunity.” Mucosal immunology (2018):
9. Cortés, Alba, Rafael Toledo, and Cinzia Cantacessi. “Classic models for new perspectives: delving into helminth–microbiota–immune system interactions.” Trends in parasitology (2018).