There is an emerging understanding that plants under biotic stress can recruit beneficial microbes in a “cry for help” strategy, and there is ample evidence that this is occurring in the case of Fusarium. Disease-recruited microbes in response to Fusarium pathogens have proven to be readily culturable and potent biocontrol agents in laboratory and greenhouse settings. Unfortunately, despite decades of work towards deploying microbes as biocontrol agents, promising laboratory and greenhouse studies have proven to be difficult to translate to the field. To overcome this limitation, we were funded by the USWBSI Transformational Sciences program to identify biocontrol microbes that are both recruited under Fusarium head blight (FHB) biotic stress and responsive to plant genotype. Our long-term goal is to use an understanding of these ecological interactions to develop an integrated management strategy leveraging microbiome-based approaches to reduce FHB on barley. The ability to breed crops with an elite ability to recruit protective microbes or microbial communities against FHB would be transformative to modern agriculture and could act in synergy with the application of biocontrols. In this presentation, I will discuss results from our massive amplicon-based metagenomic profiling of barley heads under disease pressure from FHB. This study involved sampling approximately 800 diseased and non-diseased barley heads from ten random training population genotypes grown in four nurseries across the US (Fargo ND, Ithaca NY, St. Paul MN and Kimberly ID). Amplicon sequencing profiles of 16S and ITS were used to assess the bacterial and fungal microbial community compositions, respectively. Overall, our data indicates a significant response of the microbial communities to both barley genotype and disease, supporting our initial rational. It also enables us to establish the core microbiome from barley heads in diseased and non-diseased states. I will also discuss ongoing and future directions of our research to: 1) design metagenomics-informed, screenable markers for breeding to improve FHB-antagonistic microbiome associations, 2) establish a diseased and non-diseased barley spike microbiome culture collection, and 3) develop experimentally-tractable Synthetic Communities to unravel the rules of barley microbiome assembly in the context of disease.