Contributions of intestinal protists on the human gut landscape through the lens of <i>Entamoeba</i> spp.

ABSTRACT Intestinal protists represent an underappreciated yet functionally significant component of the human gut microbiome. Historically dismissed as parasites or transient contaminants, many of these microbial eukaryotes, particularly Entamoeba spp., are now recognized as integral to gut ecosystem function and host immune homeostasis. This review examines the complex roles of Entamoeba spp. in the mammalian gut, positioning them as dynamic microbiome “landscapers” that influence host-pathogen interactions, immune tone, and microbial diversity. We explore the evolutionary adaptation of Entamoeba to the gut’s anaerobic and immunologically active environment, highlighting both pathogenic ( E. histolytica ) and non-pathogenic species ( E. dispar , E. coli ) and their distinct immunomodulatory strategies. Special attention is given to the host immune responses shaped by E. histolytica , including inflammasome activation, macrophage polarization, and suppression of protective type-2 responses. The review also details Entamoeba ’s interactions with the gut microbiota, emphasizing their capacity for selective bacterial predation, disruption or enhancement of microbial community structure, and synergistic or antagonistic relationships with commensals and pathogens alike. Methodological challenges in protist detection, genome annotation, and cultivation are discussed, alongside promising advances in sequencing, host DNA depletion, and animal modeling. Taken together, current evidence reframes Entamoeba spp. not as mere pathogens but as key ecological players whose presence can signal resilience or susceptibility within the gut ecosystem. Understanding the context-dependent functions of intestinal protists may offer new insights into microbial therapeutics, immune modulation, and disease prevention strategies.