Modulation of the Gut Microbiota of type 2 Diabetic Mice by Sodium Butyrate Attenuates Ischemic Stroke Injury

Abstract

Background: Type 2 diabetes (T2D) is a major comorbidity in patients with ischemic stroke that exacerbates brain injury. Recent studies have revealed that stroke injury can be influenced by the composition of the gut microbiota. However, the role of the gut microbiota of T2D patients in stroke injury and the potential benefits of manipulating the dysbiotic gut microbiota in T2D are unknown.Methods: To modulate the gut microbiota profile, male diabetic (Db) mice and wild-type (Wt) mice were randomized to receive either sodium butyrate (SB) or sodium chloride (NaCl, Con) in drinking water. After 4 weeks, fecal samples were collected for microbiota analysis by 16S rRNA gene sequencing. We then performed fecal microbiota transplantation (FMT) and established middle cerebral artery occlusion (MCAO) model of stroke to investigate the causative relationship between the gut microbiota and stroke injury.Results: We found that SB supplementation reduced food/water intake, fasting blood glucose levels and serum triglyceride (TG) levels in Db mice. Moreover, SB-treated Db mice displayed a different gut microbiota composition and higher levels of fecal butyrate than NaCl-treated Db mice. Twenty-four hours after cerebral ischemia/reperfusion, stroke mice that underwent FMT from SB-treated Db mice exhibited improvements in neurologic deficit scores and a smaller cerebral infarct volume than mice that underwent FMT from NaCl-treated Db mice. These improvements were accompanied by reductions in neuronal loss, apoptotic cell death, and microglial activation, increased levels of tight junction-related proteins and preservation of the endothelial glycocalyx in the ischemic brain.Conclusions: This study suggests that the gut microbiota of T2D can be modified by SB to afford neuroprotection against ischemic stroke injury.

A Review on Preclinical Models of Ischemic Stroke: Insights Into the Pathomechanisms and New Treatment Strategies

“…Indeed, FMT obtained from antibiotics-treated mice showed neuroprotective effects in preclinical stroke model [ 234 ]. Secondly, FMT collected from sodium butyrate treated mice was also reported to reverse neurological deficits and confer neuroprotection via reduction in apoptosis and neuronal loss in MCAO mice [ 235 ]. Interestingly, transplantation of young mice microbiota into the aged animals showed rapid recovery of stroke-generated problems and reduced the inflammatory processes in the gut and brain [ 236 ].…”