Fecal microbiota transplantation inhibits NF-κB/NLRP3 signaling to ameliorate ssepsis-associated encephalopathy in rats
Objective To explore the effects of fecal microbiota transplantation(FMT)on SAE in rats through the modulation of the gut microbiome.Methods Total of 30 Sprague-Dawley rats were divided(random number)into sham surgery,SAE,SAE+FMT,SAE+FMT+NF-κB agonist,and SAE+FMT+NLRP3 agonist groups.The gut microbiome,neurological function,and inflammatory responses in rats were analyzed using 16S rRNA sequencing,neurological behavioral scoring,water maze testing,Nissl staining,quantitative reverse transcription polymerase chain reaction,and western blot assays.Univariate analysis of variance for multiple samples among groups was conducted using SPSS software,with further pairwise comparisons using Tukey's test.Results(1)Compared with the sham surgery group,a reduction inα-diversity was observed in the SAE rats(P＜0.01),whereas an increase in α-diversity was noted in the SAE rats after FMT treatment(P＜0.05).A decrease in beneficial bacteria such as Bacteroidete and Clostridiales was seen in the SAE group compared to the sham group,which increased after FMT.(2)A decrease in mNSS,learning and memory abilities,and the number of neurons in the hippocampal CA1 region was noted in SAE rats compared with the sham group(P＜0.01),whereas an improvement in mNSS scores,learning and memory abilities,and neuron count was observed in SAE rats treated with FMT(P＜0.05).(3)Compared with the sham group,increased liver and kidney function indicators,inflammatory factors,blood-brain barrier proteins,NLRP3 pathway proteins,and NF-κB pathway proteins were observed in the SAE group(P＜0.05),which were reduced by FMT(P＜0.05).(4)The effects of FMT were negated after the intervention with NF-κB and NLRP3 agonists(P＜0.05).Conclusions FMT regulate the gut microbiome and inhibit the NF-κB/NLRP3 signaling pathway in the brain.This provides new insights into the treatment of SAE,emphasizing the importance of considering the gut microbiota in clinical therapy.
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