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

Abstract

Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.

Sleep Deprivation Increases the Anesthetic Potency of Sevoflurane Regardless of Duration

“…Above all, we want to explore the effects of REM sleep deprivation on anesthetic potency as the determination of LORR ED 50 required a period of 0.5-1 h though it is not too long, we do not know that if the sleep debt can be discharged during anesthesia, whereas as mentioned above, inhaled anesthetics cannot satisfy the homeostatic need for REM sleep, so we can exclude the effect of anesthetic time on our results. Also, modified multiple platform method was widely used for REM sleep deprivation [4,30,31] and it is convenient to model.…”

“…Sleep deprivation in mice was achieved by modified multiple platform method [4]. The mice were placed on 9 circular and 3.5 cm-diameter platforms in a ventilated transparent cage (50 × 30 × 17 cm, available food and water, 4 mice/cage) filled by water up to 1 cm of the platforms' surface enabling the mice to jump between the platforms.…”

Development of Research on the Etiology and Pathogenesis of Polycystic Ovary Syndrome

“…The gut microbiota produces obesity by affecting the host diet and metabolism. The intestinal flora was found to increase host appetite by reducing G protein-coupled receptor 5 activation and 44 serotonin (Zhang H, Butoyi C, Yuan GY, et al, 2023). In addition, Cani found that the intestinal microflora can participate in the regulation of adipose tissue metabolism through the LPS-eCB regulation ring, leading to obesity and abdominal fat accumulation (Cani PD, Plovier H, Hul MV, et al, 2015).…”

The gut microbiome contributes to splenomegaly and tissue inflammation in a murine model of primary biliary cholangitis

“…Further, the neonatal gut microbiota is central to spleen development (19), and germ-free mice have defective spleen myeloid cells (20). The gut microbiota also modulates systemic and splenic inflammatory cells induced by sleep deprivation and lipopolysaccharide (LPS) administration (21,22). The spleen-gut axis is further supported by the disappearance of murine intestinal immunoglobulin A (IgA)-secreting plasma cells after splenectomy (23), but additional evidence is needed to better define this interaction.…”