A long journey to the colon: The role of the small intestine microbiota in intestinal disease.

The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive 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-host interactions in the small intestine in the context of infectious and non-infectious 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-microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.

Metabolic Adaptations to Infections at the Organismal Level.

Metabolic processes occurring during host-microbiota-pathogen interactions can favorably or negatively influence host survival during infection. Defining the metabolic needs of the three players, the mechanisms through which they acquire nutrients, and whether each participant cooperates or competes with each other to meet their own metabolic demands during infection has the potential to reveal new approaches to treat disease. Here, we review topical findings in organismal metabolism and infection and highlight four emerging lines of investigation: how host-microbiota metabolic partnerships protect against infection; competition for glucose between host and pathogen; significance of infection-induced anorexia; and redefinition of the role of iron during infection. We also discuss how these discoveries shape our understanding of infection biology and their likely therapeutic value.