Avaliação da influência do metabolismo do triptofano no efeito protetor da linhagem Weissella paramesenteroides wpk4 sobre o desenvolvimento da mucosite intestinal murina induzida pelo quimioterápico 5-fluorouracil (5-fu)

Abstract

The microorganisms present in the microbiota are proving to be increasingly important for the general health of the host. It is known that the state of eubiosis is the condition in which the host is healthy, and its microbiota is in balance. On the other hand, dysbiosis occurs when the balance of the relation between the microbiota and the host is lost, resulting in possible damage to the host. The state of dysbiosis can induce different pathological situations. Intestinal mucositis caused by chemotherapy is an example of an inflammatory condition in which dysbiosis can be considered an important marker. There is robust scientific evidence that probiotics, live microorganisms that, when administered in adequate amounts, offer health benefits to the host, can be effective in controlling dysbiosis. In this context, the strain Weissella paramesenteroides WpK4, isolated from the nasopharynx of weaning pigs, has proven to be an excellent probiotic candidate, demonstrating beneficial effects in different experimental models of infection and inflammation. This bacterial strain has the tryptophan operon in its genome, and it is known that tryptophan is responsible for important cell signals for the host. Therefore, our objective to investigate whether tryptophan metabolism influences protection in a murine model of 5-FU-induced intestinal mucositis. In this case, W. paramesenteroides WpK4 has enzyme-coding sequences for tryptophan production and its catabolism, and a more detailed investigation of the metabolic profile showed the production of tryptophan (TRP), tryptamine (TAM), indole acetic acid (IAA) and indole aldehyde acid (IAld) by the strain studied. In a murine model of mucositis induction by 5- FU, oral administration of W. paramesenteroides WpK4 resulted in 100% survival, unlike the control group (administration of 0.85% saline solution), which resulted in 60% survival. A more detailed investigation of the evaluated parameters of the animals submitted to the mucositis model by 5-FU demonstrated that the W. paramesenteroides WpK4 strain protected the animals from morbidity and microbial shifts induced by chemotherapy, and improved host expression of molecules involved in the TRP metabolism, suggesting the activation of the AhR pathway by the studied strain.