Selective Packaging of miR‐22 and miR‐29 Orthologues into Extracellular Vesicles of the Porcine Whipworm Trichuris Suis

Abstract

ABSTRACT Helminths modulate host immunity, and in this respect, the porcine whipworm Trichuris suis has been explored clinically as an immunotherapy for inflammatory diseases. T. suis secretes a complex mixture of excretory/secretory products (ESP), including extracellular vesicles (EVs), nanosized membranous particles with bioactive cargoes of lipids, proteins and nucleic acids that are implicated in intercellular communication within organisms. Here, we characterise the EV protein and miRNA cargo of T. suis to identify potential roles in host–parasite communication. In contrast to EVs from clade III/V helminth species characterised to date, we show that T. suis EVs did not suppress LPS‐induced TNF production by human macrophages under the conditions tested, in contrast to non‐vesicular ESP fractions which did. By generating the first extracellular miRNA complement for T. suis and quantifying EV‐associated versus free miRNAs across larval and adult stages, we identify selective enrichment of two miRNAs in adult EVs with homology to human miR‐22‐3p and miR‐29‐3p, canonical anti‐fibrotic and tumour‐suppressor miRNAs. Functional assays in human colon cancer epithelial cells reveal that these helminth‐derived orthologues downregulate conserved oncogenic targets, indicating evolutionary conservation of their regulatory capacity. Our findings uncover a previously unrecognised axis of whipworm biology in which selective EV‐mediated export of anti‐fibrotic miRNAs has the potential to modulate host tissue remodeling independently of classical immunomodulation, with implications for understanding helminth‐driven epithelial homeostasis and cancer risk.