Beyond Koch's postulates: the pathobiome paradigm in grapevine esca disease.

Esca is one of the most damaging fungal diseases of grapevine and continues to defy Koch's postulates. Although Phaeomoniella chlamydospora, Phaeoacremonium minimum, and Fomitiporia mediterranea are consistently associated with wood necrosis in esca-symptomatic vines, they also occur in asymptomatic vines and even in apparently healthy wood tissues without visible necrosis, and single-species but also mixed-species inoculations rarely reproduce the characteristic foliar symptoms. We hypothesize that esca is best understood as a stress-mediated pathobiome disorder of the grapevine holobiont rather than a predictable outcome of specific fungal combinations, shifting focus from pathogen identity to holobiont functional state and environmental context. In this Review, we integrate evidence from community ecology, vascular biology, and multi-omics studies to link microbial community structure and activity with host hydraulics, defence, and environmental drivers. Metabarcoding and metatranscriptomics indicate that symptom expression correlates with functional reprogramming of trunk-inhabiting fungi more than their mere presence, while metabolomics and epigenomics reveal localized physiological disruption combined with systemic regulatory responses. Climatic and edaphic stresses, particularly drought, are strongly associated with holobiont destabilization and dysbiosis, altering symptom expression without necessarily modifying pathogen occurrence. We propose a temporal, multi-phase model integrating colonization history, microbiome restructuring, and host stress physiology through long-term feedbacks. This framework emerges through convergent multi-omics evidence and generates testable predictions for early detection, microbiome-informed biocontrol, and resilience-oriented vineyard management strategies.