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Overcoming Evolutionary Mismatch by Self-Treatment with Helminths: Current Practices and Experience
Abstract and Figures
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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... Despite dramatic early successes prior to 2005 at the University of Iowa, the effort to bring biota reconstitution to the clinic eventually failed, likely due in part to a lack of understanding regarding the production of helminths by pharmaceutical manufacturers [37]. Subsequently, thousands of individuals began self-treating with helminths [37,38], but the practice has not yet reached mainstream clinical use. ...
... Only within the past decade, while examining the reported outcomes of individuals self-treating with helminths, co-author Parker and colleagues observed that helminths were beneficial to neuropsychiatric function in humans [38]. Recent findings in rodent models of biota reconstitution support the importance of those organisms for mental health and function [39][40][41]. ...
... Other neuropsychiatric disorders, such as bipolar disorder, schizophrenia, and autism spectrum disorder, show hallmarks of neuroimmune dysfunction and are difficult to treat with current pharmaceutical treatments focused on the nervous system (Table 2). Systematic studies of individuals using intentional helminth exposure to reduce pathological immune reactivity indicated that the presence of helminths mitigates symptoms of both major depressive disorder and anxiety disorders [38,47]. These disorders and others can potentially be treated with biota alteration as a novel option. ...
... 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. ...
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.
... No standardized treatment protocol exists for helminth therapy, including terms such as duration of therapy, dosage, and timing (Cheng et al., 2015). Guidelines must be designed to ensure consistent and reproducible helminth administration, monitoring, and patient follow-up (Fleming and Weinstock, 2015). ...
As an alternative treatment in cancer therapy, there has been a growing interest in using helminths, such as Trichinella spiralis (T. spiralis), Echinococcus granulosus (E. granulosus), Toxocara canis (T. canis), and Taenia solium (T. solium). This study aimed to investigate the antigens and mechanisms that contribute to the anticancer properties of helminths, providing insights into how helminths may be used as a new and innovative treatment modality for cancer. The current review analyzed preclinical and clinical studies published between 2000 and 2023. The present study sought to obtain information on helminths, such as E. granulosus, T. spiralis, T. canis, and T. solium, to treat cancers of the breast, pancreas, melanoma, and leukemia by exploring databases, such as PubMed, Google Scholar, and Scopus. Studies focusing on helminth therapy against particular cancer types for in vitro and animal models were included. Several studies have shown the possibility of inhibiting breast, colon, melanoma, and leukemia tumor growth, inducing apoptosis, and modulating the tumor microenvironment with E. granulosus, T. spiralis, T. canis, and T. solium based on in vitro and animal models studies. Some studies have indicated that helminth therapy can improve survival rates, reduce tumor growth, and stimulate the immune system in cancer patients. A potential improvement in treatment outcomes can be used for combination therapies, such as antigen selection, immune profiling, and individualized approaches based on helminth therapy. Helminth therapy is an additional option for cancer treatment, emphasizing T. spiralis, E. granulosus, T. canis, and T. solium. These helminth antigens could modulate immune responses and directly cause cytotoxicity in cancer cells.
... 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. ...
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.
In this manuscript, we explore the potential therapeutic use of helminths. After analyzing helminths’ role in connection with human health from the perspective of their symbiotic and evolutionary relationship, we critically examine some studies on their therapeutic applications. In doing so, we focus on some prominent mechanisms of action and potential benefits, but also on the exaggerations and theoretical and methodological difficulties of such proposals. We conclude that further studies are needed to fully explore the potential benefits of this perspective, and we encourage the scientific community in doing so.
The avoidance of infectious disease by widespread use of 'systems hygiene', defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this 'biota alteration' leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.35; p<0.0001). Thus, it is now apparent that 'biome reconstitution', defined as the artificial re-introduction of benign, symbiotic helminths or protists into the ecosystem of the human body, is important not only for alleviation of chronic immune disease, but likely also for pandemic preparedness.
Some helminthic and protozoan infections become chronic with mild symptoms; however, they can gradually
affect the immune system and skew its balance toward antiinflammatory conditions. Noticeably, infection
with helminths is usually related to reduced cellular immune responses and a shift of T-cell responses to two
types of T helper. An inverse association was also found between the prevalence of autoimmune diseases and
helminthic infections which suggests that “helminthic therapy” might be beneficial in patients with autoim-
mune diseases. Helminthic therapy can mitigate the intensity of inflammatory responses and improve the
clinical symptoms of autoimmune diseases with minor side effects. However, some intracellular protozoan
infections will skew the immune responses toward T helper 1 type and may trigger the development of auto-
immune disease. In this chapter, we will mainly focus on this idea and will discuss the possible mechanisms
and also the challenges behind them. The main idea in helminthic therapy is the application of some parasites
and their products as immunomodulatory agents for the development of new drugs and novel optimistic
therapeutic agents for the treatment of autoimmune disease.
Inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response in the gastrointestinal tract. The number of patients with IBD has increased worldwide, especially in highly industrialized western societies. The population of patients with IBD in North America is forecasted to reach about four million by 2030; meanwhile, there is no definitive therapy for IBD. Current anti-inflammatory, immunosuppressive, or biological treatment may induce and maintain remission, but not all patients respond to these treatments. Recent studies explored parasitic helminths as a novel modality of therapy due to their potent immunoregulatory properties in humans. Research using IBD animal models infected with a helminth or administered helminth-derived products such as excretory–secretory products has been promising, and helminth–microbiota interactions exert their anti-inflammatory effects by modulating the host immunity. Recent studies also indicate that evidence that helminth-derived metabolites may play a role in anticolitic effects. Thus, the helminth shows a potential benefit for treatment against IBD. Here we review the current feasibility of “helminth therapy” from the laboratory for application in IBD management.
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.
Previous studies have compared the immune systems of wild and of laboratory rodents in an effort to determine how laboratory rodents differ from their naturally occurring relatives. This comparison serves as an indicator of what sorts of changes might exist between modern humans living in Western culture compared to our hunter-gatherer ancestors. However, immunological experiments on wild-caught animals are difficult and potentially confounded by increased levels of stress in the captive animals. In this study, the humoral immune responses of laboratory rats in a traditional laboratory environment and in an environment with enriched biodiversity were examined following immunization with a panel of antigens. Biodiversity enrichment included colonization of the laboratory animals with helminths and co-housing the laboratory animals with wild-caught rats. Increased biodiversity did not apparently affect the IgE response to peanut antigens following immunization with those antigens. However, animals housed in the enriched biodiversity setting demonstrated an increased mean humoral response to T-independent and T-dependent antigens and increased levels of "natural" antibodies directed at a xenogeneic protein and at an autologous tissue extract that were not used as immunogens.
Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders.
The field of autism research is currently divided based on a fundamental question regarding the nature of autism: Some are convinced that autism is a pandemic of modern culture, with environmental factors at the roots. Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood.
In this review, two lines of reasoning are examined which suggest that autism is indeed a pandemic of modern culture. First, given the widely appreciated derailment of immune function by modern culture, evidence that autism is strongly associated with aberrant immune function is examined. Second, evidence is reviewed indicating that autism is associated with 'triggers' that are, for the most part, a construct of modern culture. In light of this reasoning, current epidemiological evidence regarding the incidence of autism, including the role of changing awareness and diagnostic criteria, is examined. Finally, the potential role of the microbial flora (the microbiome) in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture.
It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.
We report a panel designed to open a dialog between pharmaceutical sponsors, regulatory reviewers, and other stakeholders regarding the use of social media to collect data to support the content validity of patient-reported outcome instruments in the context of medical product labeling. Multiple stakeholder perspectives were brought together to better understand the issues encountered in pursuing social media as a form of data collection to support content validity. Presenters represented a pharmaceutical sponsor of clinical trials, a regulatory reviewer from the Food and Drug Administration, and an online data platform provider. Each presenter shared its perspective on the advantages and disadvantages of using social media to collect this type of information. There was consensus that there is great potential for using social media for this purpose. There remain, however, unanswered questions that need to be addressed such as identifying which type of social media is most appropriate for data collection and ensuring that participants are representative of the target population while maintaining the advantages of anonymity provided by online platforms. The use of social media to collect evidence of content validity holds much promise. Clarification of issues that need to be addressed and accumulation of empirical evidence to address these questions are essential to moving forward.
Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Online content is a primary source of healthcare information for internet-using adults and a rich resource for health researchers. This paper explores the methodological and ethical issues of engaging in health research using social media.
A metamethod was performed on systematically selected studies that used social media as a data source for exploring public awareness and beliefs about Human Papillomaviruses (HPV) and HPV vaccination. Seven electronic databases were searched using a variety of search terms identified for each of three concepts: social media, HPV vaccine, and research method. Abstracts were assessed for eligibility of inclusion; six studies met the eligibility criteria and were subjected to content analysis. A 10-item coding scheme was developed to assess the clarity, congruence and transparency of research design, epistemological and methodological underpinnings and ethical considerations.
The designs of the six selected studies were sound, although most studies could have been more transparent about how they built in rigor to ensure the trustworthiness and credibility of findings. Statistical analysis that intended to measure trends and patterns did so without the benefit of randomized sampling and other design elements for ensuring generalizability or reproducibility of findings beyond the specified virtual community. Most researchers did not sufficiently engage virtual users in the research process or consider the risk of privacy incursion. Most studies did not seek ethical approval from an institutional research board or permission from host websites or web service providers.
The metamethod exposed missed opportunities for using the dialogical character of social media as well as a lack of attention to the unique ethical issues inherent in operating in a virtual community where social boundaries and issues of public and private are ambiguous. This suggests the need for more self-conscious and ethical research practices when using social media as a data source. Given the relative newness of virtual communities, researchers and ethics review boards must work together to develop expertise in evaluating the design of studies undertaken with virtual communities. We recommend that the principles of concern for welfare, respect for person, and justice to be applied in research using social media.
One facet of the growing social media phenomenon is the opportunity to directly appeal to prospective research participants. An example of this is Facebook advertising to defined populations. In conjunction with online data collection, social media advertising can simplify and accelerate data collection, and it can do so at greatly reduced costs. Thanks to these contemporary tools, responses can be collected at the same time from participants living in Vancouver, Toronto, and St. John’s. In this article, we describe how social media can be used for rapid and cost-effective data collection. Moreover, these methods allow researchers to directly access prospective study participants who may be otherwise difficult to reach (because of their low prevalence, their remote location, or organisational barriers). For illustrative purposes, we review methods from 2 studies: 1 of older adults with bipolar disorder and 1 of Canadian paramedics and their spouses. In both cases, participants clicked sociodemographically targeted Facebook advertisements and were directed to online study questionnaires. Based primarily on these 2 lines of research, we offer recommendations and best practices for researchers interested in utilizing social media for online recruitment and data collection. We contend that in many instances, social media may be the most effective means to recruit participants from low-prevalence and invisible populations. The majority of Canadians, and indeed much more of the world population than was previously accessible, can be reached via social media today. In addition to offering strategies to improve participant communication, we also review the limitations of social media advertising and online research.
Depression is characterized by disturbed sleep and eating, a variety of other nonspecific somatic symptoms, and significant somatic comorbidities. Why there is such close association between cognitive and somatic dysfunction in depression is nonetheless poorly understood. An explosion of research in the area of interoception—the perception and interpretation of bodily signals— over the last decade nonetheless holds promise for illuminating what have until now been obscure links between the social, cognitive–affective, and somatic features of depression. This article reviews rapidly accumulating evidence that both somatic signaling and interoception are frequently altered in depression. This includes
comparative studies showing vagus-mediated effects on depression-like behaviors in rodent models as well as studies in humans indicating both dysfunction in the neural substrates for interoception (e.g., vagus, insula, anterior cingulate cortex) and reduced sensitivity to bodily stimuli in depression. An integrative framework for organizing and interpreting this evidence is put forward which incorporates (a) multiple potential pathways to interoceptive dysfunction; (b) interaction with individual, gender, and cultural differences in interoception; and (c) a developmental psychobiological systems perspective, emphasizing likely differential susceptibility to somatic and interoceptive dysfunction across the lifespan. Combined with current theory and evidence, it is suggested that core symptoms of depression (e.g., anhedonia, social deficits) may be products of disturbed interoceptive– exteroceptive integration. More research is nonetheless needed to fully elucidate the relationship between mind, body, and social context in depression.
In just one decade, social media have revolutionized the life of many people and thus attracted much attention, not only from industry, but also academia. To understand how researchers have adopted theories, used research constructs, and developed conceptual frameworks in their studies, a systematic and structured literature review based on five leading online academic databases was conducted. A total of 46 articles on social media research were consolidated and analyzed, including empirical studies spanning from 2002 to 2011. A collection of theories/models and constructs/attributes adopted in these articles is summarized and tabulated for easy reference and comprehension of extant research results. A causal-chain framework was developed based on the input-moderator-mediator-output model to illustrate the causality between the research constructs used and the conceptualization of theoretical models/theories proposed by previous researchers. Because social media cover a wide range of research topics, the literature review may not be exhaustive. However, the proposed causal-chain framework and suggested research directions may be regarded as representative references for future research in the subject area. This is believed to be the first comprehensive literature review of social media research, and it contributes to a better understanding of the causes and effects of the adoption and usage of social media.