A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration

Aims: Sleep deprivation (SD) correlates with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. This study aimed to evaluate the roles and mechanisms of SD in inflammatory organ injury after lipopolysaccharide (LPS) administration. Main methods: Mice were intraperitoneally injected with LPS followed by 3 consecutive days of SD. The pseudo germ-free (PGF) mice received fecal microbiota transplant by being gavaged with supernatant from fecal suspension of septic mice with or without SD. The subdiaphragmatic vagotomy (SDV) or splenectomy was performed 14 days prior to LPS injection or antibiotics administration. Key findings: Post-septic SD increased the plasma levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), reduced IL-10 plasma level, increased spleen weight, and promoted inflammatory injury of the lung, liver and kidney. The relative abundance of Proteobacteria and its subgroups were increased after post-septic SD. PGF mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors did. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, splenectomy also abrogated the increase in IL-6 and TNF-alpha plasma levels and the decrease in IL-10 plasma level in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Significance: Gut microbiota-vagus nerve axis and gut microbiota-spleen axis play key roles in modulating systemic inflammation induced by SD after LPS administration.

Automated summary

The study showed that sleep deprivation exacerbates systemic inflammation after sepsis, with the involvement of the gut microbiota-vagus nerve axis and gut microbiota-spleen axis in modulating the inflammatory response.