As active members of the European COST (Cooperation on Science and Technology) Action Blastocystis under One Health (CA21105) we wish to express our concerns regarding several statements presented in the review “An Update on Blastocystis: Possible Mechanisms of Blastocystis-Mediated Colorectal Cancer” by Tocci, Das, and Sayed1. Based on our collective expertise in Blastocystis research, we wish to note that no comprehensive epidemiological, in vitro or in vivo data conclusively supports the assertions of Tocci et al.1 who suggest that a direct causal relationship between Blastocystis infection or colonisation and the development of colorectal cancer (CRC) has been established. Establising causation requires carefully designed and integrated mechanistic and epidemiological studies with appropriate controls. As outlined, such studies currently do not exist, and the claims in the review of Tocci et al.1 rely heavily on speculative interpretations of limited studies that we discuss in brief below.
Blastocystis is the most common protist in the human gut globally. More than 45 subtypes have been identified, with over 10 of these found in humans with ST3 the most prevalent globally2,3. Despite the first description of Blastocystis being published more than 110 years ago4, its clinical significance is still under debate5–7. According to the available data, when Blastocystis is detected in clinical cases it is primarily associated with gastroenterological and dermatological conditions that are related to both the host’s immune status and other components of the gut microbiota8–11. Although some studies have reported an increased prevalence of Blastocystis among cancer patients12,13, these studies do not provide any evidence or mechanistic insights that would implicate a causal role for Blastocystis in CRC. For example, it may simply be specific changes to the local environment of the gut in CRC (including treatment-induced changes in gut ecology, immune suppression, or broader dysbiosis) could explain an increased prevalence in cancer patients in some studies. An association between Blastocystis and carcinogenesis has been shown in a rat model, where urinary oxidative indices correlated with carcinogenesis were shown to be higher in rats infected with Blastocystis than in non-infected rats14. However, to our knowledge, this is the only in vivo study reported in the literature and was conducted in laboratory rodents and not humans. The Blastocystis isolate used was ST3, the most common subtype occurring in humans, but not adapted to infect rodents, which typically harbour ST4. Most importantly, this isolate was obtained from a faecal sample of a non-symptomatic individual, concentrated on a density gradient and subsequently used to infect rats with the presence of other microbes (e.g. bacteria, viruses) in the concentrate notably not excluded. Furthermore, the morphological forms presented in the study14 appear to be inconsistent with recognised Blastocystis morphotypes. On this note, Tocci and colleagues1 outline that certain Blastocystis subtypes are pathogenic. However, a detailed understanding of the genetic and phenotypic diversity of Blastocystis STs and their biological significance with respect to host health and disease is limited, and robust research data linking the disease-causing potential or pathogenicity of subtypes or morphotypes to CRC is simply not available. Based on the current literature, it is not possible to differentiate Blastocystis subtypes and/or strains as being either commensal or pathogenic, as contradictory study findings on Blastocystis subtypes and pathogenicity are widespread15–18.
Contrary to studies suggesting a role for Blastocystis in CRC, a recent study using state-of-the-art metagenomic approaches that presented data from the largest cohort studied to date (involving more than 56,000 individuals from 32 countries) has demonstrated a negative correlation between CRC and Blastocystis19. More generally, a negative correlation between Blastocystis and other diseases that involve inflammation of the gastrointestinal tract e.g. ulcerative colitis and Crohn’s Disease have been reported in independent studies20,21.
Conclusion
The history of microbial oncology, exemplified by Helicobacter pylori and gastric cancer22,23 demonstrates that microbial involvement in cancer is possible. However, in those cases, causation was only established after decades of carefully controlled epidemiological, mechanistic, and clinical studies. For Blastocystis, such a body of evidence does not currently exist, and even if we critically assess the evidence that is available, there is no credible basis for asserting that Blastocystis causes CRC in humans. Its high prevalence globally makes its detection in cancer patients unsurprising, and current studies provide, at best, speculative correlations. Importantly, premature claims of causation carry the risk of misleading clinicians, alarming patients, and diverting research away from more productive avenues. Furthermore, they undermine the nuanced view emerging from microbiome science24–27, where Blastocystis is often associated with gut health rather than disease. Whilst future research may yet clarify the potential roles of Blastocystis, whether neutral, beneficial, or detrimental, until such evidence exists, statements linking Blastocystis to cancer should be regarded as misleading and premature.
Ethics and consent statement
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Disclaimer
The views expressed in this article are those of the author(s). Publication in Open
Research does not imply endorsement by the COST ACTION funding body.
Data availability statement
No data are associated with this article.
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