Gli acidi grassi a catena corta derivati ​​dal microbiota intestinale esercitano effetti proliferativi e antiossidanti sulle cellule di Schwann

The term "gut microbiota" encompasses the collective population of microorganisms inhabiting the digestive tract, comprising various species of bacteria, archaea, fungi, and viruses. These microorganisms exert significant influence on human health, primarily by preventing intestinal infections and modulating digestion and nutrient absorption. Nonetheless, their impact extends beyond these functions to affect the overall organism, including various systems, organs, and tissues, through the production of various substances during nutrient breakdown. This study focuses on short-chain fatty acids (SCFAs), bacterial metabolites generated via the fermentation of dietary fibers and resistant starch. SCFAs have demonstrated beneficial effects in delaying disease progression such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, irritable bowel disease, chronic pain, and others. However, limited knowledge exists regarding the precise effects of SCFAs on the peripheral nervous system, including cell proliferation, survival, and nerve regeneration. Given that SCFAs are sensed by specific membrane bound receptors, including Free Fatty Acid 2 and 3 (FFAR2, FFAR3), Olfactory Receptor Family 51 Subfamily E Member 1 (Or51E1), Hydroxycarboxylic Acid Receptor 2 (HCAR) and olfactory receptor 59 (Olr59), this study first investigates the expression of SCFA receptors in peripheral nervous system cells (Schwann cells, nerve fibroblasts, sensitive neurons), showing that at the mRNA level Schwann cells express FFAR2 and FFAR3. The effects of short-chain fatty acids acetate, propionate, and butyrate on cell proliferation and resistance to oxidative stress was subsequently assessed. Initially, experiments were conducted using a cell model, the RT4-D6P2T cell line, followed by primary cultures of rat Schwann cells. Results indicate that pretreatment with butyrate or propionate confers protective effects on Schwann cells under oxidative stress conditions, accompanied by reduced reactive oxygen species (ROS) production. Moreover, the expression of antioxidant enzymes Heme Oxygenase 1 (HO1), Catalase, NAD(P)H quinone oxidoreductase-1 (NQO1) and Nuclear factor erythroid 2–Related Factor 2 (NRF2) in Schwann cells exposed to H2O2-induced oxidative stress after SCFA pretreatment was evaluated, revealing reduced expression of HO1 gene, suggesting diminished cellular stress levels and reduced requirement for high levels of protective enzyme production. Taken together these results show a positive effect of SCFAs on Schwann cell activity; subsequent studies are required to elucidate the precise mechanisms through which gut microbiota metabolites exert these effects and to determine the potential of SCFAs as treatment options for peripheral nerve disorders.