Diet has a profound effect on physiology. Over-nutrition increases the risk of disease by affecting immunity and metabolism, but caloric restriction and fasting appear to be healthful. Despite the multiple associations between diet and health, the biology behind them remains unclear.
On February 23, 2023, Filip K. Swirski's team at the Icahn School of Medicine at Mount Sinai published a study titled "Monocytes re-enter the bone marrow during fasting and alter the host response to infection" online at Immunity (IF=43). The study, titled "Monocytes re-enter the bone marrow during fasting and alter the host response to infection," was published online by Filip K. Swirski's team at Immunity (IF=43). The study found that prolonged fasting induces a stress response in the brain, which has a more negative effect on immune cells, which can be detrimental to the fight against infection and increase the risk of heart disease.
The study identified a fasting-induced switch in leukocyte migration that extended the lifespan of monocytes and altered susceptibility to disease in mice. The study found that fasting induced a rapid return of monocytes from the blood to the bone marrow during active periods. Monocyte reentry was regulated by hypothalamic-pituitary-adrenal (HPA) axis-dependent release of corticosterone, which increased CXCR4 chemokine receptors. Although the bone marrow is a safe haven for monocytes in times of nutritional deprivation, refeeding prompts mobilization and ultimately leads to an increase in monocytes from older and differently transcribed monocytes. These changes alter the response to infection. This study suggests that diet, and in particular the temporal dynamic balance of diet, regulates monocyte lifespan and thus adaptation to external stresses.
Caloric excess shortens the life span of the organism, increases systemic inflammation and the risk of cardiometabolic diseases, and exacerbates bacterial infections. Conversely, caloric restriction and fasting have been shown to be negatively associated with hypertension, atherosclerosis, diabetes, obesity, colitis, asthma, and psoriasis. Because energy intake is associated with a wide range of metabolic processes that affect physiologic function, the exact mechanisms linking diet to tissue, cellular, and molecular function remain poorly understood.
Recent studies have shown that diet affects the distribution of leukocytes throughout the body. For example, Belkaid and coworkers found that T lymphocytes move from secondary lymphoid organs to the bone marrow (BM) during caloric restriction, Hase and coworkers found that B cells leave Peyer's patches, and Merad et al. have demonstrated that fasting reduces the number of circulating monocytes in mice and humans by preventing their mobilization from the BM. Diet-dependent changes in leukocyte distribution can have a significant impact on disease outcome, particularly in response to infection, oral tolerance, tumor growth, and during experimental autoimmune encephalomyelitis.
This study focused on exploring the effects of fasting and refeeding on monocyte dynamics and homeostasis and their mechanisms. The study provides a series of events that occur during fasting and refeeding that link the HPA axis to monocytes and BM. While fasting can prevent disease in many cases, prolonged fasting and refeeding habits are limiting, or at least costly. This study found that prolonged fasting induces a stress response in the brain that has a more negative effect on immune cells, which can be detrimental to fighting off infections and increase the risk of heart disease. There is strong evidence that during starvation, various body systems shut down or are greatly reduced in a predictable order, which may reflect a hierarchy related to survival imperatives.
