Integrative Perspectives on Host–Microbiome–Parasite Interactions in Health and Disease

The human host exists as a dynamic biological system shaped by continuous interactions with resident microbial communities and parasitic organisms. While traditional models of infectious disease have focused on binary host–pathogen relationships, emerging evidence supports a more integrated triangular framework in which host, microbiome, and parasites engage in complex ecological and immunometabolic crosstalk. Within this triadic network, the microbiome establishes foundational immune and metabolic homeostasis through immune education, epithelial barrier maintenance, and colonization resistance. Parasites, in turn, deploy sophisticated immune evasion and immunomodulatory strategies that enable persistence, reshape microbial ecosystems, and recalibrate host immune responses. Concurrently, microbial communities can either restrict or facilitate parasitic colonization through niche competition, metabolite production, and immune priming. Disruption at any vertex of this triangle whether through dysbiosis, infection, or immune imbalance can propagate systemic effects that influence susceptibility to infectious, inflammatory, and metabolic diseases. Chronic parasitic infections may promote immune tolerance and plasticity, potentially mitigate autoimmune pathology while increasing vulnerability to secondary infections. Conversely, microbiome instability can predispose hosts to parasitic invasion and exacerbate immunopathology. These bidirectional and context-dependent interactions highlight the inadequacy of reductionist models and underscore the need for system-level approaches to disease biology. This review synthesizes current evidence on host–microbiome, host–parasite, and microbiome–parasite interactions, emphasizing mechanistic pathways, ecological dynamics, and translational implications. Though the multidirectional host– microbiota-parasite–relationship is still under investigation, evidence increasingly suggests that these interactions have a major influence on host health and disease outcomes.