Continuous monoculture of Rehmannia glutinosa causes severe replant disease, but how soil chemical changes related to microbiome dysfunction remains unclear. This study aimed to identify the key chemical drivers and their role in directing microbial succession during long-term monoculture. Through integrated metabolomic, elemental, and metagenomic analyses across a 10-year chronosequence, we identified a distinct chemical signature in early-stage diseased soils, characterized by accumulation of phytotoxic metabolites (e.g., beauvericin, trehalose) and elements (e.g., arsenic, copper). These chemical changes were strongly associated with and predictive of microbial community restructuring. Early-stage soils were enriched in stress-adapted taxa such as Burkholderia , which exhibited functional specialization in aromatic compound degradation. In contrast, beneficial bacteria like Methyloversatilis and the mycorrhizal fungus Tuber were suppressed. Metagenomic profiling revealed a systemic metabolic shift: early-stage soils showed enrichment in stress-response and transport pathways, whereas late-stage soils exhibited increased vitamin and cofactor metabolism. Culture-based assays confirmed the pathogenic role of fungi such as Penicillium and Fusarium in early stages, while beneficial fungi like Chaetomium became more abundant later. Our findings reveal that replant disease in R. glutinosa is characterized by a distinct soil chemical signature that correlates with a directional shift in the microbiome toward a detoxifying, nutrient-competitive state, while suppressing beneficial plant-microbe interactions. This chemical-microbial covariation provides a framework for understanding and mitigating soil sickness in R. glutinosa monoculture, and may inform studies of other continuous cropping systems. • A distinct soil chemical stress syndrome (phytotoxins & trace elements) drives early replant disease in Rehmannia glutinosa . • Soil chemistry acts as a primary filter, shaping microbial succession from stress-tolerant to vitamin-synthesizing taxa. • Pathogenic fungi ( Penicillium , Fusarium ) dominate early stages, while beneficial fungi ( Chaetomium ) increase later. • Integrated multi‑omics identifies P, Cu, and beauvericin as key discriminants of disease stages. • The chemical-microbial axis offers a mechanistic framework for managing soil sickness in continuous cropping.
Dong et al. (Fri,) studied this question.