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副干酪乳杆菌 L9 通过调节肠道菌群结构和精氨酸代谢影响实验性自身免疫性神经炎的疾病进展。

Lactobacillus paracasei L9 affects disease progression in experimental autoimmune neuritis by regulating intestinal flora structure and arginine metabolism.

机构信息

Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.

出版信息

J Neuroinflammation. 2023 May 22;20(1):122. doi: 10.1186/s12974-023-02808-8.

Abstract

BACKGROUND

Autoimmune neuropathies are common peripheral nervous system (PNS) disorders. Environmental influences and dietary components are known to affect the course of autoimmune diseases. Intestinal microorganisms can be dynamically regulated through diet, and this study combines intestinal microorganisms with diseases to open up new therapeutic ideas.

METHODS

In Lewis rats, a model of EAN was established with P0 peptide, Lactobacillus were used as treatment, serum T-cell ratio, inflammatory factors, sciatic neuropathological changes, and pathological inflammatory effects on intestinal mucosa were detected, and fecal metabolomics and 16 s microbiome analysis were performed to further explore the mechanism.

RESULTS

In the EAN rat model, Lactobacillus paracasei L9 (LP) could dynamically regulate the CD4/CD8T balance in serum, reduce serum IL-1, IL-6 and TNF-α expression levels, improve sciatic nerve demyelination and inflammatory infiltration, and reduce nervous system score. In the rat model of EAN, intestinal mucosa was damaged. Occludin and ZO-1 were downregulated. IL-1, TNF-α and Reg3γ were upregulated. LP gavage induced intestinal mucosa recovery; occludin and ZO-1 upregulation; IL-1, TNF-α and Reg3γ downregulation. Finally, metabolomics and 16 s microbiome analysis were performed, and differential metabolites were enriched with an important metabolic pathway, arginine and proline metabolism.

CONCLUSION

LP improved EAN in rats by influencing intestinal community and the lysine and proline metabolism.

摘要

背景

自身免疫性神经病变是常见的周围神经系统(PNS)疾病。环境影响和饮食成分已知会影响自身免疫性疾病的病程。肠道微生物可以通过饮食进行动态调节,本研究将肠道微生物与疾病相结合,开辟了新的治疗思路。

方法

在 P0 肽诱导的 EAN 大鼠模型中,使用鼠李糖乳杆菌作为治疗方法,检测血清 T 细胞比例、炎症因子、坐骨神经病理变化和对肠道黏膜的病理炎症影响,并进行粪便代谢组学和 16S 微生物组分析,以进一步探讨其机制。

结果

在 EAN 大鼠模型中,副干酪乳杆菌 LP 可以动态调节血清中的 CD4/CD8T 平衡,降低血清 IL-1、IL-6 和 TNF-α表达水平,改善坐骨神经脱髓鞘和炎症浸润,并降低神经功能评分。在 EAN 大鼠模型中,肠黏膜受损。occludin 和 ZO-1 下调。IL-1、TNF-α和 Reg3γ上调。LP 灌胃诱导肠黏膜恢复;occludin 和 ZO-1 上调;IL-1、TNF-α和 Reg3γ下调。最后进行代谢组学和 16S 微生物组分析,差异代谢物富集到一个重要的代谢途径,精氨酸和脯氨酸代谢。

结论

LP 通过影响肠道群落和赖氨酸和脯氨酸代谢来改善 EAN 大鼠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffd6/10204268/4ae9e0b9dd50/12974_2023_2808_Fig1_HTML.jpg

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