Old Friends Hypothesis

In an earlier article of this series, one of us (GLAT) described the so-called “Hygiene Hypothesis.” Here, we discuss further enhancements of the hypothesis. 

As discussed in the previous article, David P. Strachan, in a 1989 paper that he published in the British Medical Journal, proposed an explanation for the lower incidence of allergy in younger siblings. He hypothesized that the exposure of the younger children to the germs that their older brothers and sisters had brought home had strengthened their immune systems, predisposing them to mount the type of immune response that eliminates foreign substances, rather than the type that causes allergies. Strachan’s proposal, which later became known as the Hygiene Hypothesis, is supported by the finding that allergies are less common among the children in farming families compared to those living in more urban areas. Further, children in families that keep household pets also have been observed to have fewer allergies. The rationalization for these observations is that the children in such families are exposed to animal germs early in life, building the ability to tolerate them. Thus, improvements in sanitation and hygiene increase susceptibility to allergies as germs from siblings, animals, and environment are eradicated, as well as the immune system’s tolerance to them.

An inverse relationship has also been observed between the incidence of allergies and autoimmune disorders and infection with parasitic worms. Indeed, in a 1976 letter to Lancet, John A. Turton reported obtaining relief from his severe hay fever by intentionally infecting himself with hookworm larvae. Research in pursuit of an explanation is continuing and clinical trials are being conducted to verify the therapeutic value of purposeful infection with parasitic worms.

(It has also spawned an industry whereby companies would provide customers with parasitic worms, e.g., hookworms, for the equivalent of about P150,000 per “treatment.” Yes, the customers are to infect themselves (via the skin) every five years or so with the larvae of hookworms — parasitic worms (helminths) that can cause anemia, diarrhea, weight loss, and itchiness among many others! Another “helminthic therapy” that is being offered is in the form of pig whipworm eggs that are taken orally once every two or three weeks. We should emphasize that such “treatments” have not been approved by health regulators, here or elsewhere.)

Thus, a recent refinement of the Hygiene Hypothesis is the “Old Friends Hypothesis.” According to the latter, the presence of parasites and microbes that chronically infect us stimulates the regulatory cells which control and instruct the helper (Th1 and Th2) cells to not attack these “harmless” organisms even though they are foreign to our body. (The reader is referred to the earlier article on the Hygiene Hypothesis for a discussion of the action of helper and regulatory T cells.) These organisms are then able to grow and live inside us without eliciting an immune response. Examples of these organisms include the commensal (literally, eating together at the same table) microbes that reside in our guts (e.g., Lactobacilli), parasitic worms, and microorganisms that are found in soil, decaying matter, and untreated water (e.g., mycobacteria).

These parasitic organisms are “old friends” in that they have coexisted with us throughout our evolution. We have been in constant contact with them since way back when we were still swinging in trees and were eating freshly picked leaves and fruits and other unwashed and uncooked food. Interaction with these “old friends” through the ages undoubtedly helped shape our immune system in its present form. Living the real-life definition of “friends,” we depend on each other. Some of them help in our digestion, some produce substances that we need but which we do not produce ourselves, and some protect us from truly harmful microorganisms. They in turn need us for food and shelter. And now it seems that we need them also to regulate our immune system to prevent our getting allergies and autoimmune diseases.

As we stopped living near farms, or started drinking distilled water, we excluded our “old friends.” Now, as the immune system of our babies develops, it misses its “old friends.” Their absence inhibits the stimulation of regulatory cells, which leads to the confusion of helper cells and to uncontrolled Th1 and Th2 responses, resulting in the attack on normally innocuous substances and even on non-foreign (i.e., self) cells. Our babies become prone to allergies and autoimmune diseases.

The Old Friends Hypothesis is supported by the observation that asthma, allergies, and autoimmune diseases (e.g., multiple sclerosis, Crohn’s disease, ulcerative colitis, lupus) are almost unknown in Third World countries where people are still commonly infected with parasites. In fact, having a reunion with our “friends” through hookworm infection reduces the symptoms of asthma and other allergies and various autoimmune disorders — the basis of the P150,000 hookworm therapy. Moreover, nowadays, various products such as yogurts “with live microorganisms” and drinks that ask “okay ka ba tiyan?” abound in supermarkets. Supplements with concentrated probiotic bacteria are even available to further facilitate a happy get-together with our old and faithful “friends” in our guts.

Please don’t get this wrong. Don’t feed your children dirt to prevent them from getting allergies! We still need to avoid the harmful enemies (pathogens) but, at the same time, we need to stay in touch with beneficial friends. The Old Friends Hypothesis implies that what is needed in the proper regulation of our immune system is not the quantity of exposure (the number of “friends” we have), but rather the quality of exposure (the type of “friends” we mingle with).

Indeed, “a faithful friend is the medicine of life” — Ecclesiasticus 6.16.

Who knows — maybe after thorough study, re-infestation with our “old friends” will become standard treatment for allergies and other irregularities of our immune system. Better yet, if we could find out how those “friends” manage to regulate our immune system, we might be able to design therapies for allergy and autoimmune disease that do not require infection with parasitic worms.

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Glaiza Tan is a 2008 BS MBB summa cum laude graduate of the University of the Philippines Diliman and is currently an MS student in Molecular Medicine at the St. Luke’s College of Medicine-William H. Quasha Memorial. Eduardo A. Padlan is a corresponding member of the NAST and is an adjunct professor in the Marine Science Institute, College of Science, University of the Philippines Diliman. They can be reached at [email protected] and [email protected], respectively. Neither author has any professional, personal or financial interests in companies that provide helminthic therapy.