Blastocystis is one of the most prevalent intestinal protists, colonizing more than one billion people worldwide. Nevertheless, its role in health and disease remains blurred. Blastocystis was historically dismissed as a commensal. However, it can have pathogenic or protective effects. This review synthesizes molecular epidemiology, clinical research, microbiome studies, and experimental models through a One Health approach to reassess Blastocystis. Subtypes ST1-ST4 are dominant in humans, but their health outcomes vary. ST4 is associated with irritable bowel syndrome and inflammatory responses. However, it has also been shown to exert protective effects on murine colitis models. In contrast, ST3 is frequently detected in healthy individuals with a diverse gut microbiota. Blastocystis is also widespread in animals, untreated water, wastewater, and food, reflecting complex transmission dynamics and raising concerns in low- and middle-income countries where poverty-related exposures increase risks. Diagnostic advances have improved detection, although mixed infections and inconsistent clinical interpretations persist, and treatment guidelines remain absent. Rather than being a uniform pathogen or benign passenger, Blastocystis emerges as a context-dependent component of the gut ecosystem and environmental microbiota. Its ubiquity across humans, animals, and the environment requires integrated surveillance, subtype-informed research, and interdisciplinary health strategies. Recognizing the ecological complexity of Blastocystis is essential for equitable diagnostics, treatment, and public health responses within the One Health framework.

Charles University 3rd Faculty of Medicine Prague Czech Republic

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