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Gastrointestinal infection is a leading cause of gut diseases attracting global health concerns. The emerging antimicrobial resistance in enteric pathogens drives the search of viable and renewable alternatives to antibiotics for the health of both human beings and animals. Spore-forming probiotic Bacillus have received extensively interests for their multiple health benefits, including the restoration of microbiota dysbiosis and the reduction of drug-resistant pathogens. These promising benefits are mainly attributed to the activity of structurally diverse Bacillus-derived metabolites, such as antibacterial compounds, short-chain fatty acids, and other small molecules. Such metabolites show the capacity to directly target either the individual or community of bacterial pathogens, and to potentiate both host cells and gut microbiota. The better understanding of the mechanisms by which probiotic Bacillus and the metabolites modulate the metabolism of hosts and microbiota will advance the screening and development of probiotic Bacillus. In this review, we discuss the interaction among probiotic Bacillus, microbiota and host, and summarize the Bacillus-derived metabolites that act as key players in such interactions, shedding light on the mechanistic understanding of probiotic Bacillus against enteric bacterial infections. [ABSTRACT FROM AUTHOR]