Modulatory role of Blastocystis-derived solubilized antigens in colorectal carcinogenesis: A systematic review

Colorectal cancer develops through complex interactions among genetic alterations, immune responses, and the intestinal microenvironment. Increasing evidence suggests that intestinal parasites may also contribute to colorectal carcinogenesis (CRC). Blastocystis sp. (Blastocystis) is one of the most common intestinal protozoans worldwide. Although its role in disease remains controversial, it has been associated with chronic inflammation and disruption of normal gut homoeostasis. Therefore, this systematic review aimed to summarise the current experimental evidence on the immunomodulatory effects and potential role of Blastocystis solubilized antigens (BSA) in CRC. A systematic literature search was conducted following PRISMA guidelines in PubMed, Scopus, Web of Science, and CINAHL. Six eligible experimental studies investigating the effects of BSA on colorectal cancer cell lines (HCT116 and HT-29) and peripheral blood mononuclear cells (PBMCs) were included. The included studies demonstrated that BSA influences several biological processes associated with CRC. Symptomatic isolates, particularly Subtype 3 (ST3), showed the strongest biological effects by promoting colorectal cancer cell proliferation, increasing the expression of pro-inflammatory and tumour-associated mediators, and reducing p53 gene expression. BSA also increased the gene expression of NF-κB and Nrf2 and reduced the effectiveness of the chemotherapeutic agent 5-fluorouracil (5-FU). In addition, BSA altered cytokine production in PBMCs, with chemotherapy-treated colorectal cancer patients exhibiting reduced immune responsiveness compared to healthy individuals. Overall, the available evidence suggests that Blastocystis, particularly ST3, may contribute to CRC through immune modulation, activation of tumour-related cellular pathways, and reduced chemotherapy sensitivity. However, the limited number of available studies highlights the need for further experimental and clinical investigations to clarify the role of Blastocystis in CRC and its impact on treatment outcomes.