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Plants depend on their associated microbiota to improve their nutritional status and their tolerance to environmental stresses. Several reports focused on the interaction between a single plant and a microbe, while plant changes during multiple associations have been poorly explored. We investigated the local and systemic effects on wheat after colonization with two Plant-Growth-Promoting-Bacteria (PGPB) (Azospirillum brasilense, Paraburkholderia graminis) alone or associated with an arbuscular mycorrhizal fungus (AMF). To address this issue, phenotypic, transcriptomic, proteomic and biochemical analyses were combined. Despite several common processes are triggered by both PGPB, they differently impacted the plant growth. We have also investigated whether the bipartite (wheat-PGPB) or tripartite (wheat-PGPB-AMF) interactions may have a bioprotective effect on the leaf pathogen Xanthomonas translucens. Omics results show that A. brasilense down regulates the plant defense and increases wheat susceptibility, which, however, is mitigated in the presence of AMF. The combination of P. graminis and AMF triggers a plant immune response leading to a lesion reduction. The synergic effects exhibited by the AMF and the PGPB in counteracting Xanthomonas are mostly based on the amplification of jasmonate signaling pathway. Overall, our findings point out that wheat finely modulates its growth/defense trade-off depending on the selected microbial pairing.