Reduced appetite during infection is known as sickness associated anorexia (SAA), and it is one of several sick behaviors that have evolved to be shared by all living things, from insects to humans. The question of whether such calorie restriction aids or hinders recovery is still up for dispute among academics. The conventional wisdom that malnutrition and infection feed off one another typically describes long-term malnutrition that results in deficiencies in energy and protein. But since the same inflammatory cytokines that cause immunological responses also cause SAA-induced energy restriction, it is most likely a part of an evolutionary defense mechanism against infection and host protection.
The relationship between organismal nutrition and the outcome of infection is complex and interconnected. First, the body needs enough energy to start and maintain an effective immune response in addition to maintaining overall bodily functions. Second, the quantity of energy consumed influences the host’s metabolic state, which in turn influences a number of downstream mediators, such as those that regulate inflammation and tissue stress. Third, the fitness and replication of pathogens are directly impacted by the host’s overall nutritional status as well as particular cellular metabolic conditions.
Metabolic needs greatly rise during acute infection including the requirement for glucose, fatty acids and amino acids to power defence and maintenance processes. In order to preserve physiological function by limiting tissue and organ damage, disease tolerance must be balanced with disease resistance, which entails inactivating the pathogen. Immune cell activation, a shift to aerobic glycolysis, and participation in anabolic programs are all components of immune resistance to infection, while disease tolerance primarily depends on catabolic processes like fatty acid oxidation (FAO) and autophagy to protect organs.
During an infection’s acute phase response, the induction of catabolic processes that break down larger molecules into smaller biomolecules and metabolic intermediates to meet the increased energy and biomass demands necessary for an effective host response is the net systemic metabolic change. The same inflammatory mediators that cause infection-induced catabolic processes also cause SAA, which lowers energy intake. This may serve three purposes, including promoting maintenance-focused programs that lower inflammation, assisting in the adaptation to a catabolic, lipid-utilizing state, and producing fasting mediators like ketone bodies that guard against tissue stress and ultimately increase disease tolerance.
Hyperglycemia, or elevated blood glucose, is another metabolic change frequently observed in human infections. This condition is brought on by a disruption in the metabolism of glycogen and severe insulin resistance. It causes both metabolic and energetic failures and is one of the most well-known metabolic dysregulations in sepsis patients. Both human patients and animal models of sepsis initially exhibit a hyperglycaemic response. Consequently, glucose is diverted to immune cells, enhancing immunological function and aerobic glycolysis. However, excessive immune activation brought on by increased glycolysis may be more detrimental than beneficial.
Anorexia and peripheral glucose consumption are two characteristics that contribute to hypoglycemia, or low glucose levels, in the later stages of sepsis. Low glucose levels in sepsis patients are likewise associated with poor outcomes and organ failure, as is the case with hyperglycemia. Additional research has demonstrated that acute infection-associated anorexia, which is characterized by decreased food intake and consequently low blood glucose levels, is essential for surviving bacterial sepsis but may be harmful in the event of viral inflammation. It is currently unclear how hypoglycemia contributes to infection based on data from a number of clinical investigations. Whether hypoglycemia exacerbates sepsis, is a consequence of severe sepsis, or promotes metabolic adaptation needs further investigation.
Adapted from:
Jindal, J., Hill, J., Harte, J., Dunachie, S. J., & Kronsteiner, B. (2024). Starvation and infection: The role of sickness-associated anorexia in metabolic adaptation during acute infection. Metabolism: clinical and experimental, 161, 156035. https://doi.org/10.1016/j.metabol.2024.156035.