Co-infection of Cystoisospora suis with enterotoxigenic Escherichia coli synergistically increases pathogenicity in weaned piglets.

Abstract

BACKGROUND: While Cystoisospora suis is well established as a primary pathogen in suckling piglets, it can also infect weaned piglets. In this context, we investigated its co-infection with enterotoxigenic Escherichia coli (ETEC), a major cause of post-weaning diarrhea. METHODS: Weaned piglets were randomly divided into four groups: a negative control group (NC), an ETEC single-infection group (EC), a C. suis single-infection group (CS), and a co-infection group (EC-CS). Following infection, clinical symptoms were recorded, and samples were collected to evaluate intestinal histopathological damage, expression of tight junction protein genes, inflammatory cytokine levels, and gut microbiota changes. RESULTS: Compared to single-infection groups, piglets in the co-infection group exhibited more severe diarrhea, growth retardation, and intestinal damage, characterized by near-total loss of villus and crypt structures. Co-infection significantly impaired intestinal barrier function, as evidenced by a marked downregulation of claudin-1 messenger RNA (mRNA) expression compared to both single-infection groups, and triggered more intense local and systemic inflammatory responses. 16S ribosomal RNA (rRNA) sequencing revealed that co-infection exacerbated gut microbiota dysbiosis and promoted the proliferation of pathogenic bacteria. CONCLUSIONS: Co-infection with C. suis and ETEC exerts a synergistic pathogenic effect in weaned piglets. The mechanism involves a vicious cycle of intestinal barrier disruption, microbiota dysbiosis, and amplified inflammatory responses. These findings provide a novel theoretical basis for the clinical prevention and control of complex intestinal co-infections.