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Indeed, many infectious and non\u2010infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non\u2010invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota\u2013host interactions in the small intestine in the context of infectious and non\u2010infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host\u2013microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non\u2010infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non\u2010infectious diseases of the gastrointestinal (GI) tract. 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