The Microbiome Within a Microbe: Rethinking Blastocystis Biology.

Blastocystis spp., one of the most prevalent microeukaryotes in the human gut, has long puzzled researchers with its ambiguous role in health and disease. Decades-old microscopy studies reported bacterial- and viral-like particles within Blastocystis spp. cells, but these findings have been mainly overlooked. Comparable associations in other protozoa, such as those between Trichomonas vaginalis and Mycoplasma, as well as protozoan-virus interactions, are known to influence metabolism, immune evasion, and ecological fitness. Here, we revisit these neglected observations in Blastocystis spp., framing them within the holobiont concept and proposing that this protist may host its own microbial consortium. We also propose potential mechanisms, ecological implications, and modern experimental strategies-from organ-on-a-chip to single-cell multi-omics-to rigorously test this hypothesis. Recognizing Blastocystis spp. as a possible "microbiome within a microbe" could transform our understanding of its biology and its place in gut microbial ecology.