Use of dexmedetomidine to alleviate intestinal ischemia-reperfusion injury via intestinal microbiota modulation in mice

Abstract

Background: Intestinal ischemia-reperfusion (I/R) injury is a serious condition with unacceptable mortality rates. Our previous study revealed a protective effect of dexmedetomidine (DEX) on intestinal I/R injury, but its underlying mechanism remains unclear. Gut microbiota imbalance is associated with the progression of I/R injury. We hypothesized that DEX would attenuate intestinal I/R injury via modulating gut microbiota. Methods: An I/R injury model was established in C57BL/6 mice in the presence or absence of DEX preconditioning. Some mice were treated with antibiotics to deplete intestinal bacteria. Fecal microbiota transplantation (FMT) was performed by transplanting the feces of DEX-pretreated mice into a new batch of I/R mice. We analyzed the expression of Bacteroidetes and Firmicutes in feces, survival rate, and inflammatory cytokines. Results: DEX reversed I/R-induced bacterial abnormalities by increasing the ratio of Firmicutes to Bacteroidetes [DEX + I/R 3.02±0.36 vs. normal saline (NS) + I/R 0.82±0.15; 95% CI: 0.80-3.60; P<0.05] and was accompanied by increased 72-hour survival (0.40±0.16 vs. 0.10±0.09; P<0.05). The protective effect of DEX did not significantly differ from that of DEX + antibiotics. Furthermore, the bacteria of the DEXpretreated mice decreased the release of inflammatory factors.Conclusions: This study revealed that DEX can alleviate intestinal I/R injury through a microbiotarelated mechanism, providing a potential avenue for the management of intestinal I/R injury.

Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action

“…This can be attested by recent literature that shows that the response of murine neutrophils to I/R injury is different based on host colonization [ 35 ]. This notion is also supported by a recent study that demonstrated a protective effect of dexmedetomidine in alleviating intestinal I/R injury by modulating the gut flora [ 36 , 37 ]. The aforementioned studies taken in sum constitute powerful evidence that the response of the gut to I/R injury can be explained by the “complex crosstalk” between the “the intestinal epithelium, the intestinal immune system and the intestine’s endogenous bacteria”[ 26 ].…”

Attenuation of intestinal ischemia-reperfusion-injury by anesthetics: a potentially protective effect of anesthetic management in experimental studies

“…Some new protective mechanisms of DEX in intestinal IRI in animal models have been reported in recent years. DEX can attenuate intestinal I/R injury by decreasing ferroptosis and pyroptosis, enhancing mitophagy, promoting the mitochondrial localization of TERT, and microbiota-related mechanisms ( Liu et al, 2021 ; Zhang et al, 2021 ; Dong et al, 2022 ; Hu et al, 2022 ; Hou et al, 2023 ). These findings provide new experimental evidence supporting the protective effect of DEX against intestinal IRI and a unique insight into the clinical use of DEX, which has positive significance for DEX administration in the perioperative period.…”

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

“…For clinical surgeons, IIRI has been a persistent issue for a significant period (3). Because of intestine's high energy requirements and continuous exposure to a varying blood supply, surgery patients are prone to IIRI, which can lead to intestinal anastomotic leakage, prolonged hospitalization, and increased morbidity and mortality (4,5). On the other hand, the pathophysiology of IIRI is complex and involves a variety of interconnected mechanisms, including oxidative stress, inflammation, necrosis, and apoptotic cell death (6,7).…”