The Role of Nucleotides in the Immune and Gastrointestinal Systems

Abstract

Nucleotides are low molecular weight biological molecules key to biochemical processes. Sources include de novo synthesis, recovery via salvage mechanisms, and dietary intakes. Although endogenous production serves as the main nucleotide source, evidence suggests that exogenous sources are essential to immune competence, intestinal development, and recovery. Dietary nucleotides serve a marked role in rapidly proliferating cells where they are necessary for optimal function. Accordingly, dietary nucleotides are deemed conditionally essential in the presence of various physiological stresses, including growth and development, recovery from injury, infection, and certain disease states. Clinical studies that evaluated nutrition formulations of nucleotides in combination with other specific nutrient substances demonstrated improved clinical outcomes in patients characterized as critically ill, injured, immune suppressed, or with chronic gastrointestinal conditions. However, conclusions regarding specific benefits of nucleotides are limited. Scientific substantiation of nucleotide supplementation in infant formula has been reported to improve the maturation and development of the intestinal tract as well as immune function. All medical nutrition products except for one immune-modulating formulation are devoid of nucleotides. In an effort to build on this, the current review presents the data to support potential clinical applications for nucleotides in enteral nutrition that may contribute to improved outcomes in physiologically stressed patients.

The role of DNA damage response in zebrafish and cellular models of Diamond Blackfan Anemia

“…Nucleoside mixtures are safe, and many infant formulas already include nucleosides and nucleotides (Singhal et al, 2010). Nucleoside supplementation in enteral nutrition has been shown to improve outcomes in physiologically stressed individuals (Hess and Greenberg, 2012). …”

Effects of Enteral Immunonutrition in Patients Undergoing Pancreaticoduodenectomy: A Meta-Analysis of Randomized Controlled Trials

“…Omega-3 fatty acids have anti-inflammatory effects that can promote wound healing, and enhance the adaptive immune response [36]. RNA can improve hypoimmunity and enhance host defenses in patients with cancer [37]. Recently, researchers have found that immunonutrition is more effective than standard nutrition in enhancing inflammation, improving the host immune state, and short- has also recommended the use of EIN in surgical patients with upper gastrointestinal cancer to reduce postoperative infectious complications [38], but the effects of EIN in patients undergoing PD are still unclear.…”

Physiological Effects of Nucleotide Supplementation on Resistance Exercise Stress in Men and Women

“…Nucleotides produced through de novo synthesis are often insufficient to meet the needs of rapidly proliferating tissues, and therefore, the salvage pathway is required to synthesize nucleotides from exogenous sources (12). As such, dietary nucleotides are necessary to maintain immune function, tissue growth, and cellular repair (8,12,17). Exercise is a stressful and damaging stimulus, significantly increasing demands on the immune system and temporarily attenuating immune cell function.…”

“…N ucleotides are essential to nearly all biological processes including DNA and RNA synthesis, coenzyme synthesis, energy metabolism, cellular signaling, and protein homeostasis (8,14,17). Nucleotides produced through de novo synthesis are often insufficient to meet the needs of rapidly proliferating tissues, and therefore, the salvage pathway is required to synthesize nucleotides from exogenous sources (12).…”