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Overcoming Evolutionary Mismatch by Self-Treatment with Helminths: Current Practices and Experience

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Background. Biome depletion, or loss of biodiversity from the ecosystem of the human body, is a major "evolutionary mismatch" underlying a variety of inflammatory diseases in Western populations. Enhancing biodiversity via exposure to helminths has effectively treated immune diseases in a variety of experimental animal models and in a few published studies involving human subjects. Purpose. This study probes another untapped resource for helminthic therapy: the methods and outcomes reported by individuals currently self-treating with helminths. Procedures. Helminth providers were interviewed, surveys were collected from self-treaters, and publically available information was compiled. Results. More than 250 anecdotal experiences of self-treatment were assessed, and the total number of individuals worldwide currently self-treating was estimated at between 6,000 and 7,000. A wide range of inflammation- related diseases, including inflammatory bowel disease, allergies, and autoimmunity, were effectively treated. Conclusions. This study finds that the therapy is being refined through experience and is now expanding to treat widespread neuropsychiatric problems such as depression, anxiety, migraine headaches, bipolar disorder, and perhaps Parkinson's disease.
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... Specifically, we tested the hypothesis that the presence of the rat tapeworm, Hymenolepis diminuta, might alter the onset and progression of breast cancer in the mice. Hymenolepis diminuta was selected because (a) it is currently being used for helminth therapy in humans, with apparently promising results [25][26][27], and (b) it has been shown to eliminate pathologic inflammation in laboratory mice [28]. The organism is benign and beneficial [29] in its native host, Rattus norvegicus, and fails to develop to maturity in both mice and humans. ...
... Although several helminths are currently being used for therapeutic purposes in humans, no systematic search of an ideal candidate helminth has been conducted [30]. Nevertheless, work in the field suggests that a wide range of helminths, either cestodes or nematodes, work in a similar fashion to ameliorate chronic, pathologic inflammation [26,31]. However, at the present time, H. diminuta is the only helminth that has been studied as a potential therapeutic agent in both humans [25][26][27] and in laboratory animals [28,29,32]. ...
... Nevertheless, work in the field suggests that a wide range of helminths, either cestodes or nematodes, work in a similar fashion to ameliorate chronic, pathologic inflammation [26,31]. However, at the present time, H. diminuta is the only helminth that has been studied as a potential therapeutic agent in both humans [25][26][27] and in laboratory animals [28,29,32]. Further, given that not all helminths are beneficial [33,34], it was important to select a helminth such as H. diminuta that has an established therapeutic benefit. ...
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Background and objectives An individual’s risk of breast cancer is profoundly affected by evolutionary mismatch. Mismatches in Western society known to increase the risk of breast cancer include a sedentary lifestyle and reproductive factors. Biota alteration, characterized by a loss of biodiversity from the ecosystem of the human body as a result of Western society, is a mismatch known to increase the risk of a variety of inflammation-related diseases, including colitis-associated colon cancer. However, the effect of biota alteration on breast cancer has not been evaluated. Methodology In this study, we utilized the C3(1)-TAg mouse model of breast cancer to evaluate the role of biota alteration in the development of breast cancer. This model has been used to recapitulate the role of exercise and pregnancy in reducing the risk of breast cancer. C3(1)-TAg mice were treated with Hymenolepis diminuta, a benign helminth that has been shown to reverse the effects of biota alteration in animal models. Results No effect of the helminth H. diminuta was observed. Neither the latency nor tumor growth was affected by the therapy, and no significant effects on tumor transcriptome were observed based on RNAseq analysis. Conclusions and implications These findings suggest that biota alteration, although known to affect a variety of Western-associated diseases, might not be a significant factor in the high rate of breast cancer observed in Western societies. Lay summary An almost complete loss of intestinal worms in high-income countries has led to increases in allergic disorders, autoimmune conditions, and perhaps colon cancer. However, in this study, results using laboratory mice suggest that loss of intestinal worms might not be associated with breast cancer.
... Further, numerous studies have elucidated a variety of immunological mechanisms underlying helminth therapy, including production of a wide range of helminth-derived immunoregulatory molecules, induction of regulatory networks, and activation of otherwise dormant immune components [15][16][17][18][19][20]. In light of this information, it is perhaps unsurprising that thousands of individuals today use helminths to treat their chronic inflammatory conditions [13,21,22]. Systematic data gathering from people "self-treating" with helminths was first suggested by Flowers and Hopkins in 2013 [23] as an effective method for obtaining information regarding the effects of therapeutic helminths on patients with chronic immune related disease. ...
... Previous studies collecting information from individuals self-treating with helminths [13,21,22] have encompassed four helminths, a wide range of disease, and more than 1000 individual cases. Data collection methods include surveys, interviews with helminth providers, and interviews with physicians who have experience observing patients who are self-treating. ...
... Prior studies evaluating the outcomes of individuals self-treating with helminths [13,21,22] have utilized a series of methods, including surveys for self-treating individuals, surveys for physicians who monitor self-treating individuals, and interviews with producers and suppliers of helminths. In some cases, survival bias and response bias have been either eliminated or quantified, and several lines of evidence, outlined in the Discussion, indicate that placebo and nocebo effects contribute minimally to reported outcomes. ...
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The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.
... More recently, studies in animal models by Maizels et al. [19,20] as well as prospective clinical studies by Correale et al. [21][22][23] have extended the apparently beneficial role of exposure to helminths to include prevention of autoimmune conditions [24,25]. Further, emerging evidence indicates that exposure to helminths also helps prevent or alleviate a range of inflammationassociated neuropsychiatric disorders, including chronic fatigue syndrome, anxiety disorders and major depressive disorders [26][27][28][29]. ...
... disorders, like autoimmune diseases, are probably associated with biota alteration [26][27][28][29][46][47][48][49]. Although the idea that viral infection can trigger neuropsychiatric disorders is difficult to assess, some evidence exists [50,51]. ...
... However, since the reproduction of helminths is much more easily controlled than is the reproduction of protists, helminths rather than protists are preferred for development as a therapeutic. Systematic sociomedical studies evaluating the effects of helminth therapy on individuals engaging in self-treatment with helminths confirms studies in laboratory animals and indicates that the therapy is indeed very effective and safe for a range of common allergic, autoimmune and neuropsychiatric conditions [27,28,68]. ...
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Suboptimal understanding of concepts related to hygiene by the general public, clinicians, and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as COVID-19, hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems, and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of SARS-CoV-2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes summarizing this information are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers.
... As can be seen, the absence of complex eukaryotic symbionts causes a very profound shift in immune markers (Fig. 2, Table 1). Work by Correale from Argentina [5,6,76] as well as our own studies [77,78] show that re-introduction of complex eukaryotic symbionts halts the progression of (relapsing-remitting) MS, for example through direct modulation of the host immune system [76]. This provides conclusive evidence supporting the idea that loss of eukaryotic symbionts is the pivotal evolutionary mismatch that underlies the pathogenesis and progression of MS. ...
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Multiple sclerosis (MS), a neurological autoimmune disorder, has recently been linked to neuro-inflammatory influences from the gut. In this review, we address the idea that evolutionary mismatches could affect the pathogenesis of MS via the gut microbiota. The evolution of symbiosis as well as the recent introduction of evolutionary mismatches is considered, and evidence regarding the impact of diet on the MS-associated microbiota is evaluated. Distinctive microbial community compositions associated with the gut microbiota of MS patients are difficult to identify, and substantial study-to-study variation and even larger variations between individual profiles of MS patients are observed. Furthermore, although some dietary changes impact the progression of MS, MS-associated features of microbiota were found to be not necessarily associated with diet per se. In addition, immune function in MS patients potentially drives changes in microbial composition directly, in at least some individuals. Finally, assessment of evolutionary histories of animals with their gut symbionts suggests that the impact of evolutionary mismatch on the microbiota is less concerning than mismatches affecting helminths and protists. These observations suggest that the benefits of an anti-inflammatory diet for patients with MS may not be mediated by the microbiota per se. Furthermore, any alteration of the microbiota found in association with MS may be an effect rather than a cause. This conclusion is consistent with other studies indicating that a loss of complex eukaryotic symbionts, including helminths and protists, is a pivotal evolutionary mismatch that potentiates the increased prevalence of autoimmunity within a population.
... However, he does argue that, because exposure to particular helminths and protists is not consistent, no absolute codependence is likely to emerge. Further, as predicted by Flowers and Hopkins [1], the systematic study of the failures and successes of more than a thousand individuals self-treating with various species of helminths has provided considerable insight into the effects of helminths on human immune function and health [2][3][4]. ...
... Meanwhile, IL-33 also promotes age-related macular degeneration (Xi et al., 2016), another late-life inflammaging-linked disease. Anecdotal evidence from home-users of live helminth therapy suggests that old friend helminths may also provide protection against Parkinson's disease and depression, although whether the latter includes geriatric depression is not known (Cheng et al., 2015). Both Parkinson's disease and geriatric depression are considered to be inflammaging-linked conditions (Teixeira et al., 2012;Calabrese et al., 2018). ...
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Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, probiotic therapies that restore ‘old friend’ microbes and helminths have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, which contributes to a range of age-related diseases, including cardiovascular disease, dementia, and cancer. Interestingly, Crowe et al., 2020 recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?
... So far, H. diminuta has mainly been tested in animals, and the beneficial effect of suppressing inflammation has been shown for several disease models, such as Crohn's disease, rheumatoid arthritis, and an autism-type neurocognitive disorder [36][37][38][39]; however, this effect was not detected in all studies [40,41]. Additionally, reports from the community of so-called self-treaters suggest a high efficacy for H. diminuta (more than 60%) in more than 50 different chronic diseases associated with inflammation and also describe minimal side effects [42,43]. Despite differences in the nature of the immune response and the length of colonization among rodent models (rats versus mice), the beneficial effect of H. diminuta on intestinal inflammation has been observed in both cases [39,44]. ...
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Colonization by the benign tapeworm, Hymenolepis diminuta, has been associated with a reduction in intestinal inflammation and changes in bacterial microbiota. However, the role of microbiota in the tapeworm anti-inflammatory effect is not yet clear, and the aim of this study was to determine whether disruption of the microflora during worm colonization can affect the course of intestinal inflammation. We added a phase for disrupting the intestinal microbiota using antibiotics to the experimental design for which we previously demonstrated the protective effect of H. diminuta. We monitored the immunological markers, clinical parameters, bacterial microbiota, and histological changes in the colon of rats. After a combination of colonization, antibiotics, and colitis induction, we had four differently affected experimental groups. We observed a different course of the immune response in each group, but no protective effect was found. Rats treated with colonization and antibiotics showed a strong induction of the Th2 response as well as a significant change in microbial diversity. The microbial results also revealed differences in the richness and abundance of some bacterial taxa, influenced by various factors. Our data suggest that interactions between the tapeworm and bacteria may have a major impact on its protective effect.
Chapter
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