Parasitic Worms, Food Allergies, and a Case of Mistaken Identity

Earthworms are slimy and wiggly, but kinda cute. I don’t have a worm farm or anything, but if I see a worm stuck on the sidewalk, I’ll give it a ride to the dirt so it doesn’t dry out. Overall, I think earthworms are A-okay. There is another group of worms, however, called helminths. These are better known as parasitic worms and are a solid 0/10 on my scale of animals I like. These are the worms that cause trichinellosis/trichinosis (from undercooked pork), heartworms in dogs, tapeworms, nematodes, and many, many more. About 2 billion people have helminth infections worldwide, mostly in low-income countries in tropical and subtropical regions.^[1,2] Untreated helminth infections can lead to childhood development problems, malnutrition, blood problems, tissue damage, and death.^[3] Basically, helminths are certified super gross, and our bodies have evolved to get rid of these unwelcome pests as quickly as possible. The mechanism we use to get rid of helminths is called a type 2 immune response or type 2 inflammation.

A type 1 immune response stops microorganisms (viruses, bacteria, fungi…) that try to reproduce inside the body.^[3] Type 2 immune responses, by contrast, aim to both kick helminths out and repair the damage caused by these relatively big worms (tapeworms can be up to 75 feet long in extreme cases).^[3,4] This manifests as inflammation, immune cells swarming the area, increased collagen and mucus production, and increased wound repair.^[3,5,6] The response tends to be particularly aggressive and helminth worms suppress inflammation.^[2,3] Scientists suspect that mammals like humans have lived with helminth infections for so long that we evolved to “rely” on them to maintain our inflammatory homeostasis.^[2] Modern hygiene, clean water, and sanitation have made helminth infection increasingly rare in the United States.^[2] As a result, our type 2 immune response can be too aggressive: a solution looking for a problem.^[2]

Eosinophilic esophagitis (EoE) is a chronic allergic disease driven by type 2 immune responses.^[7,8] It is defined by having a large number of immune cells called eosinophils in the throat tissue (aka the esophagus).^[5] Eosinophils are immune cells that specialize in fighting big parasites like helminths. Rates of EoE have been rising in the United States and are five times higher than they were in 2009, changing from a rare disease to a common cause of distress in the esophagus.^[7] The exact causes of EoE remain  unclear, but risk factors include age, genetics, conditions at birth, and environmental factors.^[5,9,10] At some point, the cells that line the throat are disrupted and mistakenly identify parts of food as dangerous.^[5,10] Food allergens stimulate inflammatory cells, the cellular barrier of the throat is disrupted, and a type 2 immune response occurs.^[5,10] Though eosinophilic esophagitis is defined (and named) by eosinophils, there is a lot more going on than just some wayward immune cells.^[8]

Eosinophils aren’t normally found in the esophagus, so before we find them there a lot of things have to happen.^[5] In a type 2 immune response, the innate immune system first mistakes normal items as dangerous cells, proteins, or chemicals.^[5,10] Cells on the border of the throat then sound the alarm by releasing loads of signaling molecules.^[5] Signaling molecules are detected by immune cells, which amplify the signal and start causing inflammation.^[5] Two major T-cell types, Natural Killer T (NKT) and T helper 2 (Th2) cells, are big players in active EoE and are thought to drive the type 2 immune response.^[8] During active EoE, the type 2 immune response does what it does best: cause inflammation, tell immune cells to swarm the area, increase collagen and mucus production, and increase wound repair - but this time without having anything dangerous to attack or fix!^[3,5,6] The result is throat barrier dysfunction, eosinophils where they don’t need to be, immune dysregulation, changes to the microbiome, and tissue remodeling (fibrosis, a long-term problem).^[5] To the EoE sufferer, they experience a menagerie of unpleasant symptoms:^[10]

• Vomiting
• Pain in the gut and throat
• Difficulty swallowing
• Food getting stuck in the throat
• Food refusal
• Failure to thrive (in children)

What can be done? The goal of treatment is to improve quality of life by suppressing the type 2 immune response and preventing fibrosis.^[10] Dietary therapy can be a successful, non-medical solution for many people with EoE. In general, sufferers will eliminate a few common allergens from their diet such as milk and wheat/gluten, and reintroduce them slowly - hopefully finding which foods trigger their immune system.^[11] This can be successful, though it can be hard to maintain, especially if there are multiple food triggers.^[11] Medical treatments include topical corticosteroids to reduce inflammation and proton pump inhibitors, which reduce stomach acid and may help reduce some signaling molecules in the esophagus.^[11] Some researchers have also suggested that people may benefit from intentionally infecting themselves with low levels of helminths to bring the immune system in balance, but that’s 100% too gross and uncontrolled for me (and U.S. regulators). Instead, newer medications, including ones currently in clinical trials, are modeled after helminth immune suppression systems by blocking signaling molecules and suppressing immune cell activity in throat tissue. These medications suppress specific components of the immune system using antibodies, which can make them more precise and potentially reduce side effects, compared with broader immunosuppressive therapies.^[5]

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] Wright JE, Werkman M, Dunn JC, Anderson RM. Current epidemiological evidence for predisposition to high or low intensity human helminth infection: a systematic review. Parasites & vectors. 2018 Jan 31;11(1):65. https://doi.org/10.1186/s13071-018-2656-4

[2] Chen J, Gong Y, Chen Q, Li S, Zhou Y. Global burden of soil-transmitted helminth infections, 1990-2021. Infectious Diseases of Poverty. 2024 Oct 10;13(05):68-77. https://doi.org/10.1186/s40249-024-01238-9

[3] Gause WC, Wynn TA, Allen JE. Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nature Reviews Immunology. 2013 Aug;13(8):607-14. https://www.nature.com/articles/nri3476

[4] Scholz T, Garcia HH, Kuchta R, Wicht B. Update on the human broad tapeworm (genus Diphyllobothrium), including clinical relevance. Clinical microbiology reviews. 2009 Jan;22(1):146-60. https://doi.org/10.1128/CMR.00033-08

[5] Ogulur I, Mitamura Y, Yazici D, Pat Y, Ardicli S, Li M, D’Avino P, Beha C, Babayev H, Zhao B, Zeyneloglu C. Type 2 immunity in allergic diseases. Cellular & molecular immunology. 2025 Mar;22(3):211-42. https://www.nature.com/articles/s41423-025-01261-2

[6] Pulendran B, Artis D. New paradigms in type 2 immunity. Science. 2012 Jul 27;337(6093):431-5. https://doi.org/10.1126/science.1221064

[7] Thel HL, Anderson C, Xue AZ, Jensen ET, Dellon ES. Prevalence and costs of eosinophilic esophagitis in the United States. Clinical Gastroenterology and Hepatology. 2025 Feb 1;23(2):272-80. https://doi.org/10.1016/j.cgh.2024.09.031

[8] Cui J, Yu L, Wang R, Gui Y. Dysregulated IL-2 signaling and T-cell subset shifts are associated with eosinophilic esophagitis activity. Biochemistry and Biophysics Reports. 2026 Sep 1;47:102768. https://doi.org/10.1016/j.bbrep.2026.102768

[9] Khokhar D, Marella S, Idelman G, Chang JW, Chehade M, Hogan SP. Eosinophilic esophagitis: Immune mechanisms and therapeutic targets. Clinical & Experimental Allergy. 2022 Oct;52(10):1142-56. https://doi.org/10.1111/cea.14196

[10] Votto M, De Filippo M, Caimmi S, Indolfi C, Raffaele A, Tosca MA, Marseglia GL, Licari A. A practical update on pediatric eosinophilic esophagitis. Children. 2023 Sep 28;10(10):1620. https://doi.org/10.3390/children10101620

[11] Feo-Ortega S, Lucendo AJ. Evidence-based treatments for eosinophilic esophagitis: insights for the clinician. Therapeutic advances in gastroenterology. 2022 Jan;15:17562848211068665. https://doi.org/10.1177/17562848211068665