Pathogenic mechanisms of Enterocytozoon hepatopenaei from the parasite–gut microbiome–shrimp (Litopenaeus vannamei) physiology axis

Currently, owing to the static comparison between paired healthy and Enterocytozoon hepatopenaei (EHP) infected shrimp (Litopenaeus vannamei), how and to what extent the gut functional potentials respond to increasing severity of EHP infection are unclear. To close this knowledge gap, the gut microbiomes of normal, longish, medium and short sized adult shrimp were characterized by metagenomic sequencing. Shrimp digestive activity was suppressed, while immune activity was induced in EHP infected cohorts compared with healthy shrimp. Increasing severity of EHP infection gradually suppressed gut α-diversity, while diversified potential pathogens and virulence factors (VFs). In addition, dysbiosis in the compositional and functional structures of gut microbiota, and network stability among differential species linearly escalated along increasing severity of EHP infection. Accordingly, we identified 24 EHP-discriminatory species that contributed an overall 83.3% accuracy in diagnosing the infected severity of EHP without false negatives. The potentials of diverse functional pathways involved in metabolism, degradation, and biosynthesis were suppressed in EHP infected shrimp compared with healthy controls. Among them, map00630 glyoxylate and dicarboxylate metabolism and map00280 valine, leucine and isoleucine degradation consistently depleted in EHP infected individuals, which in turn dampened their digestive activity and anti-inflammatory response. In particular, EHP infection diversified VFs directly affected shrimp gut microbiome. Collectively, we propose a conceptual model to infer the pathogenic mechanisms of EHP from the parasite–gut microbiome–shrimp physiology axis.