{Reference Type}: Journal Article {Title}: Flavonoid synthesis is crucial for Trichoderma asperellum-induced systemic resistance to root-knot nematodes in tomato plants. {Author}: Zheng F;Fu Y;Yu P;Qin C;Guo T;Xu H;Chen J;Ahammed GJ;Liu A;Chen S; {Journal}: Plant Physiol Biochem {Volume}: 212 {Issue}: 0 {Year}: 2024 Jul 9 {Factor}: 5.437 {DOI}: 10.1016/j.plaphy.2024.108706 {Abstract}: Trichoderma spp. can enhance plant resistance against a wide range of biotic stressors. However, the fundamental mechanisms by which Trichoderma enhances plant resistance against Meloidogyne incognita, known as root-knot nematodes (RKNs), are still unclear. Here, we identified a strain of Trichoderma asperellum (T141) that could effectively suppress RKN infestation in tomato (Solanum lycopersicum L.). Nematode infestation led to an increase in the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) in roots but pre-inoculation with T141 significantly decreased oxidative stress. The reduction in ROS and MDA was accompanied by an increase in the activity of antioxidant enzymes and the accumulation of flavonoids and phenols. Moreover, split root test-based analysis showed that T141 inoculation in local roots before RKN inoculation increased the concentration of phytohormone jasmonate (JA) and the transcripts of JA synthesis and signaling-related genes in distant roots. UPLC-MS/MS-based metabolomics analysis identified 1051 differentially accumulated metabolites (DAMs) across 4 pairwise comparisons in root division test, including 81 flavonoids. Notably, 180 DAMs were found in comparison between RKN and T141-RKN, whereas KEGG annotation and enrichment analysis showed that the secondary metabolic pathways, especially the flavonoid biosynthesis, played a key role in the T141-induced systemic resistance to RKNs. The role of up-regulated flavonoids in RKN mortality was further verified by in vitro experiments with the exogenous treatment of kaempferol, hesperidin and rutin on J2-stage RKNs. Our results revealed a critical mechanism by which T141 induced resistance of tomato plants against the RKNs by systemically promoting secondary metabolism in distant roots.