Association of gut microbiota in the pathogenesis of acute respiratory distress syndrome and possible pharmacotherapy by sphingosine-1-phosphate

The Acute Respiratory Distress Syndrome (ARDS) is one of the major heterogeneous clinical manifestations of severe respiratory failure developing in response to pathogenetic mechanisms and several inflammatory insults. The translocation of gut microbiota has a crucial impact on the pathogenesis of ARDS. Hence, a deeper understanding of the interplay of the gut microbiota would allow shedding valuable insights into both the pathogenesis of ARDS and the development of effective therapeutic interventions. Moreover, the modulation of gut-lung axis could also play a pivotal role in minimizing the lung dysbiosis with gut microbiota. There is little question that greater study of the gut-lung axis in critically ill patients is required to establish causal links between the shifted microbiota, infections, inflammation, and acute lung damage. It is worth mentioning that the lack of effective preventative measures is one of the main reasons for the increased mortality rate of 30-40% in ARDS patients. Some antibiotics and nanosized drugs showed positive results in ARDS management to some extent in pre-clinical or even first stages of clinical trials but large-scale results had been controversial. However, Sphingosine-1-Phosphate (S1P) showed hopeful results in ARDS patients by facilitating both systemic and endothelial integrity. Numerous investigations have shown the immunological connection between the gastrointestinal tract and the respiratory system. As the SphKs /S1P /S1PL metabolic pathway is associated with a wide variety of human illnesses (including respiratory diseases), it should come as no surprise that influencing intracellular S1P levels would have therapeutic promise in reducing the severity of lung diseases like ARDS.