Gut microbiota-derived butyric acid protected against secondary brain injury after SAH by inhibiting neuronal pyroptosis and regulating gut microbiota composition (Murine assays)

ABSTRACT:

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with a poor prognosis. Accumulating studies have reported that gut microbiota contributes to the pathophysiology of several central nervous system diseases. However, whether SAH can change gut microbiota composition and affected gut microbiota is involved in the development of secondary brain injury following SAH remains unclear.

METHODS: A retrospective case-control study was performed in unruptured intracranial aneurysm (UIA, CTL) and ruptured intracranial aneurysm (SAH) patients. Patients' fecal and serum samples were collected and sequenced by metagenome and metabolome. The experimental SAH mice models were established, and their feces and serum were also analyzed by 16S rRNA and metabolic sequencing. Fecal microbiota from SAH patients and mice was transplanted to ABX mice to investigate the relationship between the gut microbiota and secondary brain injury following SAH.

RESULTS: SAH seriously influenced gut microbiota composition and significantly increased the relative abundance of the genus Escherichia. SAH also considerably reduced the production of gut microbiota-derived butyric acid. Furthermore, SAH-induced gut microbiota dysbiosis aggravated brain injury and cognitive deficits in ABX mice by promoting inflammatory response. Sodium butyrate (NaB) administration protected against secondary brain injury following SAH by inhibiting pyroptosis-related neuroinflammation, which is mediated by NLRP1/Caspase-1/GSDMD and Caspase-3/GSDME signaling pathways. NaB drinking pretreatment also alleviated secondary brain injury following SAH by increasing the relative abundance of butyric acid-producing bacteria, such as Dubosiella and Faecalibaculum, and decreasing the Escherichia abundance.

CONCLUSION: SAH contributed to gut microbiota dysbiosis and changed gut microbiota exacerbated secondary brain injury after SAH. Supplement with gut microbiota-derived butyric acid protected against brain injury following SAH by inhibiting NLRP1/Caspase-1/GSDMD and Caspase-3/GSDME-mediated neuronal pyroptosis.

Linked studies:

UPLC-MS/MS assays of murine samples are reported in this study.

UPLC-MS/MS assays of human samples are reported in MTBLS9087.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Bin Yuan 

PROVIDER: MTBLS9100 | MetaboLights | 2024-07-09

REPOSITORIES: MetaboLights