ROLE OF INTESTINAL FLORA DYSBIOSIS IN PM2.5 EXPOSURE-MEDIATED NEUROTOXICITY IN RATS AND AURICULARIAN POLYSACCHARIDE INTERVENTION

Xiaojun Chen^{1, 3, #}, Kexin Zhang^{1, #}, Shuang Li¹, Shujuan Meng⁴, Hao Zhu¹, Yanshu Zhang^{1, 2, *}

¹School of Public Health, North China University of Science and Technology, Tangshan, China 063210 - ²Experimental Animal Center, North China University of Science and Technology, Tangshan, China 063210 - ³Gong ren Hospital of Caofeidian District, Tangshan, China 063210 - ⁴Hongci hospital, Tangshan, China 063000 

Objective: To implore the role of gut flora in PM2.5 exposure inducing neurotoxicity of rats.

Methods: 64 SD rats were randomly divided into control group, PM2.5-exposed group , low-dose intervention group (intervention A) and a high-dose intervention group (intervention B).We examined their neurobehavioral changes and gathered the blood serum and brain tissue, ELISA was used to determined the protein contents of IL-1β, IL-10, IL-17, BDNF, and TGF-β, Real-time PCR was applied to measure the mRNA expression of IL-17, IL-1β and TNF-α in the hippocampus. High-throughput sequencing quantified intestinal flora composition from fecal samples. 

Results: PM2.5 exposure markedly disrupted neurocognitive function that was partially reversed by AP treatment. Compared with the control group, of IL-1β and TNF-α mRNA expression in PM2.5 exposed group were significantly increased. In addition, the auricularian polysaccharide intervention group showed a significant decrease in terms for IL-1β and TNF-α mRNA expression . Meanwhile, the content of IL-17, IL-1β and TNF-α in PM2.5 exposure group  increased than that of the control group. Content of IL-17 and TNF-α  decreased in auricularian polysaccharide intervention group relatived to PM2.5 exposure group, however, IL-1β had no significant differation compared to PM2.5 exposerd group .Compared with the control group, the content of IL-17 in the PM2.5 exposure group was significantly increased and the IL-10 content showed a decreased trend in expression. Following auricularian polysaccharide intervention, the content of IL-17 decreased, and the expression of IL-10 and TNF-α increased in two treatment groups; High-throughput sequencing showed that the abundance index (chao1) and diversity index (Shannon) of intestinal flora were higher in controls relative to PM2.5 exposed animals. All reads were clustered into 1506 OTUs (operational taxonomic units). The dominant community of taxonomic compositions at the phylum level were firmicutes, bacteroidetes, actinobactric, proteobacteria, Verrucomicrobia and tenerientes, actinobactric, proteobacteria and tenerientes all increasedin the PM2.5 exposed group relatived to the control group, firmicutes, and bacteroidetes declined. Bacteroidetes in the auricularian polysaccharide intervention group was four-fold increase as compared with PM2.5 exposure group.Clustering analysis showed that the primary genus were adlercreutzia, leacobacter and oscillospira in PM2.5 exposed group,acinetobacter,roseburia,bacteroides, fimicutes, vibrio, chloroflexi, and akkermansiaand in the auricularian polysaccharide intervention groups ,Gut microbial composition was significantly disrupted by PM2.5 exposure. 

Conclusion:  PM2.5 exposure disrupted neurocognitive capabilities that depended on altered intestinal flora and inflammatory mediator. Early auricularian polysaccharide intervention retarded to decrease CNS injury following PM2.5 exposure.