Enemy or ally? Fasting as an essential regulator of immune responses. Issue 5 (May 2021) - Wilhelm, Christoph
Abstract : Nutrition is essential for supplying an organism with sufficient energy to maintain its bodily functions. Apart from serving as an energy supply, the immunomodulatory effects of diet are emerging as a central aspect of human health. The latest evidence suggests that dietary restriction may play an important regulatory role by influencing the activation and effector functions of immune cells. However, depending on the context, nutrient restriction may have both pathogenic and beneficial effects. Here, we discuss the diverse roles of fasting programs, including ketogenesis in infection and chronic inflammation, aiming to clarify their detrimental and/or beneficial effects. Understanding these differences may help identify conditions under which dietary interventions might serve as putative effective approaches to treat various diseases. Highlights: Disease-induced anorexia is a behavioral change employed by the host upon microbial infection that induces dietray restriction by decreasing food consumption. Recent experimental data utilizing force feeding in infected mice supports the notion that anorexic behavior is a fundamental host metabolic program that can mediate either detrimental or beneficial context-dependent effects, based on the type of pathogenic challenge model. Growing evidence support the hypothesis that dietary restriction and fasting can modulate protective and pathogenic immune functions, thus improving chronic inflammation without impacting host defense against parasitic or viral infections. The ketogenic diet (KD) is a dietary intervention efficiently used to mimic fasting which induces distinct metabolic alterations in host metabolism. Recent advances have highlighted the protective effect of KD in autoimmune, inflammatory, or viral diseases, and its potential as a single/complementary candidate therapeutic approach in the clinic.