High fructose diet: A risk factor for immune system dysregulation

Excessive intake of sweets is a predisposing factor for metabolic disorders, and fructose, as one of the major dietary sugars in the diet, has been shown to be a major cause of obesity, diabetes, and metabolic syndrome. These disorders are usually associated with immune dysfunction. Therefore, exploring the effects of a high fructose diet on the immune system may provide insight into the underlying mechanisms of these diseases. We synthesized the available evidence to suggest that excessive fructose intake disrupts the body's immune homeostasis by promoting immune cell metabolic rearrangements, alterations in gut microbial community structure, and intestinal barrier permeability. Indeed, not only does fructose itself affect immune system homeostasis, but its metabolites also have a profound influence. The metabolites from fructolysis are mainly produced in the small intestine and liver and subsequently enter the systemic circulation. Elevated levels of fructose metabolites, such as uric acid, FFAs, and lactate, are closely associated with oxidative stress and local tissue and organ inflammatory responses. In this review, we will focus on the link between fructose and inflammatory responses. In the meanwhile, we will also briefly summarize the studies of cancer development and immune escape mediated by fructose, as it might be beneficial for cancer immunotherapy.