Helminthic Therapy: Worms as Medicine? Possible Uses in Ulcerative Colitis and Crohn Disease

Helminths are worm-like organisms that can reside in humans and animals and have been a part of our, and our human ancestor’s, gastrointestinal biome for thousands of years (1). However, with the advent of modern hygiene practices (flush toilets, sewage systems, wearing shoes, etc.) and anti-helminthic drugs, these organisms have become less prevalent. In many cases this is beneficial and potentially life-saving, however, it has sparked the question - is there potential harm in irradicating all helminths?

This has led to a discussion about their potential benefits in addressing various health conditions. Dr. Mary Pardee and Dr. Natalie Scheeler explore the concept of helminthic therapy, its historical context, different types of helminths, and intriguing research around their potential benefits.

"Helminthic therapy explores the idea that our modern lifestyle, marked by a reduction in intestinal worms, may contribute to the rise of autoimmune, inflammatory, and allergic disorders." Dr. Natalie Scheeler

The Historical Context

Helminths were once a common part of the gut microbiome, but factors like hygiene, public sanitation, and food preparation methods in the 19th century led to a decline in their prevalence. The introduction of antihelminthic drugs in the 20th century further reduced their numbers. This shift sparked interest in exploring the consequences of losing these organisms from our internal ecosystems.

The Hygiene and Old Friends Hypothesis

Enter the hygiene hypothesis, a concept suggesting that exposure to certain microbes during our early years helps develop a robust immune system. This hypothesis was further refined in the early 2000s to specify that it is not necessarily the common cold or relatively new infections that help inform our immune system, but instead, the microbes that were present in the hunter-gatherer times when our immune systems were evolving (2). Could the absence of these "old friends" in our modern lives be linked to the rise in autoimmune diseases and allergies? 

Mechanisms of Action

Helminths are thought to upregulate regulatory T cells (T regs), the cells responsible for regulating our body’s immune response. Sometimes compared to a manager, T reg cells help prevent overreactions and inappropriate reactions that we commonly see in autoimmune, allergic, and inflammatory conditions (3).

Differentiating Helminths from ParasitesWhile parasites typically imply harm, more commonly helminths have a commensal relationship (helminth benefits, human is unaffected). In the four helminths discussed, there is a potentially mutualistic relationship (both the human and the helminth benefit). Helminthic therapy challenges the conventional view of these organisms as harmful by exploring their potential benefits in modulating the immune system.

Types of Helminths

While there are estimated as many as 300,000 species, there are four currently accepted as potential mutualists - Necatur americanus (NA), Trichuris suis (TS), Trichuris trichiura (TT), and Hymenolepis diminuta (HDC) (4). Each type may offer different benefits, and the choice of helminth depends on the desired outcome and the specific health condition being addressed.

What conditions are being researched

Helminthic therapy is being studied for conditions involving the immune system, such as autoimmune diseases, inflammatory disorders, allergies, neuropsychiatric conditions, and metabolic disorders. Research suggests potential benefits in conditions like ulcerative colitis, Crohn's disease, celiac disease, multiple sclerosis, and even asthma.

Research for IBD

Several studies have explored the potential of helminthic therapy for inflammatory bowel disease. A Cochrane review in 2014, focusing on Trichuris suis in subjects with ulcerative colitis and Crohn's disease, showed promising results in terms of remission and clinical improvement (5). However, due to the limited number of participants and studies available, the Cochrane review determined there is not enough information to conclude the safety and efficacy of using helminths as treatment. A more recent study, again investigating the use of Trichuris suis in active Crohn’s disease did not show a clinically significant improvement over placebo for clinical remission or response (6).  

Unfortunately, the benefit of helminths in randomized controlled trials are not as clear and exciting as some of the anecdotal evidence from the self-treating community. This could be due to most clinical trials lasting between 6-12 weeks, and with helminths, we typically expect benefit anywhere from 3-24 months. 

Safety and Contraindications

While helminthic therapy shows promise, it's crucial to consider safety and tolerability. Mild to moderate abdominal symptoms and elevated eosinophil counts are common, emphasizing the importance of careful monitoring and appropriate dosing(4). Further, there are theoretical contraindications with certain conditions like severe coronary artery disease, those with structuring of the small intestine, and history of certain cancers.

Dr. Scheeler’s Experience

Dr. Scheeler chose to self-treat w/undergo Neicator americanus helminth therapy, starting with a relatively small dose of five and gradually increasing to 20 in her second dose. The increase, however, came with its challenges, leading to a condition known as "worm flu" characterized by abdominal pain and digestive changes several weeks after inoculation. She emphasizes the importance of going "low and slow" in helminth therapy to manage potential side effects effectively.

Helminthic therapy opens a new frontier in understanding the intricate relationship between our immune system and these once-common inhabitants of our gut. While more research is needed to establish safety and efficacy conclusively, the potential benefits observed in various studies and anecdotal reports offer hope for alternative approaches to managing certain health conditions.

Citations

1. Cox FE. History of human parasitology [published correction appears in Clin Microbiol Rev. 2003 Jan;16(1):174.]. Clin Microbiol Rev. 2002;15(4):595-612. doi:10.1128/CMR.15.4.595-612.2002

2. Rook GAW. The old friends hypothesis: evolution, immunoregulation and essential microbial inputs. Front Allergy. 2023;4:1220481. Published 2023 Sep 12. doi:10.3389/falgy.2023.1220481

3. Helmby H. Human helminth therapy to treat inflammatory disorders - where do we stand?. BMC Immunol. 2015;16:12. Published 2015 Mar 26. doi:10.1186/s12865-015-0074-3

4. National Research Council (US); Avise JC, Hubbell SP, Ayala FJ, editors. In the Light of Evolution: Volume II: Biodiversity and Extinction. Washington (DC): National Academies Press (US); 2008. 4, Homage to Linnaeus: How Many Parasites? How Many Hosts? Available from: https://www.ncbi.nlm.nih.gov/books/NBK214895/

5. Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD009400. DOI: 10.1002/14651858.CD009400.pub2

6. Schölmerich J, Fellermann K, Seibold FW, et al. A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in Active Crohn's Disease. J Crohns Colitis. 2017;11(4):390-399. doi:10.1093/ecco-jcc/jjw184

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