Metabolic Adaptations to Infections at the Organismal Level

Abstract

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.

Keywords: anorexia; cooperative defenses; host-microbiota-pathogen interactions; immunometabolism; infection; organismal level.

Figure 1:. Host-microbiota metabolic partnerships protect the host against infections

Wildtype microbiota produce an array of beneficial metabolites that protect the host from infection and dysbiotic microbiota. However, this benefit is highly dependent on the presence of the right diet, which serves to maintain an abundance of health-promoting microbes and provides the substrates needed for the generation of beneficial metabolites.

Figure 2:. Host and pathogen duel for glucose during infection

Many types of immune cells switch to aerobic glycolysis upon infection, a necessary change to potentiate the immune response. In parallel, several pathogenic microbes also enter glycolysis following infection, and this change is largely required to induce their virulence programs. This sets up a competition for glucose between host and pathogen.

Figure 3:. The effects of anorexia during infection are pathogen-specific

Anorexia, a host sickness behavior, can be beneficial or detrimental to the host depending on the infection, presumably as a result of how different infections affect host physiologies in unique ways.

Figure 4:. New perspectives on the role of iron during infection

Recent studies suggest that the role of iron during infection is more complex and context-dependent than the originally envisioned, simple tug-of-war.