Metabolic Adaptations to Infections at the Organismal Level

Immunometabolic interactions between host and microbiota protect from and boost defenses against infection, at a cost. Immune cells and pathogen enter glycolysis early during the course of infection, setting up a competition for glucose between host and pathogen. Infection-induced anorexia can be beneficial or detrimental to the host depending on the specific pathogen. Hosts must balance opposing metabolic adaptations in order to simultaneously potentiate immune function and promote tissue tolerance during infection. A host can promote its own survival by metabolically cooperating with a pathogen during infection. 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. 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. cooperative defense strategy that promotes pathogen fitness within the host by dampening its virulent behavior (e.g., metabolic bribery of pathogen by the host). responsible for breaking down fatty acids into acetyl-CoA molecules in order to produce energy. cooperative defense strategy that protects host tissues from the damage caused by infection. imbalance in the microbial communities of the host (changes in composition, abundance, and or diversity) associated with disease. metabolic pathway that breaks down glucose to release energy in the form of ATP. It offers a key benefit in that it also generates intermediates for the synthesis of nucleotides, amino acids, and fatty acids. field that examines the interplay between immunological and metabolic processes. multiprotein complexes of the innate immune system that are responsible for the activation of inflammatory responses. refers to a state of unresponsiveness to insulin, which blocks cells from taking up glucose from the blood and results in elevated blood glucose concentration. four criteria to establish a causative relationship between a microbe and a disease. amount of material required to kill 50% of the test population. subset of fatty acids produced by the microbiota during the fermentation of dietary fiber in the gastrointestinal tract. collection of stereotypic behavioral responses induced by infection that are highly conserved across species, including anorexia, lethargy, somnolence, fever, and social withdrawal, among others. refers to the adoption of glycolysis rather than oxidative phosphorylation in the presence of oxygen for the production of energy. Also referred to as aerobic glycolysis. heterogeneous tissue that functions to collect, store, and then release lipids.