From association to causality: microbial metabolites, redox signaling, and crop stress tolerance

Root-associated microbial metabolites and symbiotic signals have been increasingly used to explain crop tolerance to biotic and abiotic stress; however, the causal link between microbial biosynthetic potential and a defined plant physiological response often remains unclear. Biosynthetic gene cluster prediction, culture-filtrate bioactivity, whole-inoculant phenotyping, in situ metabolite detection, and genetic validation provide different and complementary forms of evidence that are not interchangeable proofs of metabolite function. This review examines selected siderophores, cyclic lipopeptides, phenazines, 2,4-diacetylphloroglucinol, pyrrolnitrin, volatile organic compounds, lipochitooligosaccharide symbiotic signals, indolic compounds, and mechanistically characterized actinomycete metabolites. Evidence is evaluated against defined outputs in crop nutrition, root development, immunity, ion homeostasis, and metabolite-linked reactive oxygen species (ROS)/Ca 2+ /nitric oxide (NO) and thiol-redox regulation, with downstream significance for photosynthesis and yield protection in plants. Examples that combine several, but not all, evidence domains include 2,4-diacetylphloroglucinol-mediated rhizosphere disease suppression, receptor-dependent lipochitooligosaccharide signaling, genetically linked pteridic-acid biosynthesis with purified-compound bioactivity, and the Enterobacter sp. SA187/2-keto-4-methylthiobutyric acid–ethylene signaling axis. In contrast, many volatile organic compound and cyclic lipopeptide claims remain strongest in closed or controlled systems, where exposure, dose, and niche persistence differ from field conditions. To distinguish among these levels of evidence, we introduce a six-domain evidence profile: biosynthetic potential, chemically verified production, in situ occurrence and exposure, dose-realistic bioactivity of a defined compound, pathway perturbation with rescue, and field exposure coupled to crop benefit. The framework complements microbiome-causality frameworks, chemical-identification confidence systems, and commercialization roadmaps. Reporting the six domains separately, rather than combining them into a single score, identifies the next evidence gap for each system while maintaining mechanistic confidence distinct from commercialization readiness.