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In knowledge discovery, experts frequently need to combine knowledge from different domains to get new insights and derive new conclusions. Intelligent systems should support the experts in the search for relationships between concepts from different domains, where huge amounts of possible combinations require the systems to be efficient but also sufficiently general, open and interactive to enable the experts to creatively guide the discovery process. The paper proposes a cross-domain literature mining methodology that achieves this functionality by combining the functionality of two complementary text mining tools: clustering and topic ontology creation tool OntoGen and cross-domain bridging terms exploration tool CrossBee. Focusing on outlier documents identified by OntoGen contributes to the efficiency, while CrossBee allows for flexible and user-friendly bridging concepts exploration and identification. The proposed approach, which is domain independent and can support cross-domain knowledge discovery in any field of science, is illustrated on a biomedical case study dealing with Alzheimer’s disease, one of the most threatening age-related diseases, deteriorating lives of numerous individuals and challenging the ageing society as a whole. By applying the proposed methodology to Alzheimer’s disease and gut microbiota PubMed articles, we have identified Nitric oxide synthase (NOS) as a potentially valuable link between these two domains. The results support the hypothesis of neuroinflammatory nature of Alzheimer’s disease, and is indicative for the quest for identifying strategies to control nitric oxide-associated pathways in the periphery and in the brain. By addressing common mediators of inflammation using literature-based discovery, we have succeeded to uncover previously unidentified molecular links between Alzheimer’s disease and gut microbiota with a multi-target therapeutic potential. [ABSTRACT FROM AUTHOR]