Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation

Abstract

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

Screening for depression and anxiety in lung cancer patients: A real‐world study using GAD‐7 and HADS

“…Similar mechanisms were indicated by experiments in mice with lung cancer 32 . Alcohol exposure regulates gut microbiota and mediates anxiety and depression through NLRP3‐mediated neuroinflammation 33,34 …”

“…32 Alcohol exposure regulates gut microbiota and mediates anxiety and depression through NLRP3-mediated neuroinflammation. 33,34 This analysis not only illuminates the potential mechanisms affecting mental well-being but also provides valuable insights for clinical practice. Depression and anxiety significantly affect patient prognosis, and there is a concerted effort to alleviate such distress.…”

RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection

“…More recently, the molecular basis of memory formation has also been shown to involve innate immune sensing of endogenous genomic damage induced by neural activity 50 . In the context of disease, pathogen sensors and inflammatory cytokines have been implicated in a variety of neurologic and behavioral outcomes [51][52][53][54][55] , including sickness behavior [56][57][58] , and inflammation generally is known to drive pathologic processes in neurons including aberrant synaptic pruning 6,59,60 , excitotoxicity 23,61,62 , and epileptogenesis 63,64 . Our results describe a nexus of neuroimmune signaling in which activation of RIPK3 dampens neuronal excitability, which in turn promotes survival in the presence of excitotoxic levels of glutamate during CNS viral infection.…”

Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder

“…However, the role of the in ammasome in psychiatric disorders such as MDD is less well understood. Numerous preclinical studies have reported that activation of the NLRP3 in ammasome is associated with depressive-like behaviors in rodents [19][20][21][22][23][24] . Nevertheless, there is a paucity of in ammasome-focused research in clinical populations with only a handful of small (n < 50) human studies published to date.…”