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副干酪乳杆菌 SD1 和鼠李糖乳杆菌 SD11 的益生菌可减轻链脲佐菌素诱导的 1 型糖尿病小鼠的炎症和β细胞死亡。

Probiotics of Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 attenuate inflammation and β-cell death in streptozotocin-induced type 1 diabetic mice.

机构信息

Faculty of Science, Division of Health and Applied Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

出版信息

PLoS One. 2023 Apr 11;18(4):e0284303. doi: 10.1371/journal.pone.0284303. eCollection 2023.

DOI:10.1371/journal.pone.0284303
PMID:37040355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10089358/
Abstract

Probiotics provide health benefits in various aspects and are believed to modulate the immune system by balancing gut microbiota homeostasis, termed the "microbiota-immune axis". Recent evidence supports that several Lactobacillus strains possess glucose-lowering and anti-inflammatory effects in an animal model of type 1 diabetes (T1D). Although probiotics of Lacticaseibacillus paracasei SD1 (SD1) and Lacticaseibacillus rhamnosus SD11 (SD11) exert human oral health benefits by reducing harmful bacterial populations, their clinical application regarding hypoglycemic-related traits as well as the underlying mechanisms are still lacking. In this report, we used multiple low doses of streptozotocin (STZ)-induced diabetic BALB/c mice to explore the effects of SD1 and SD11 supplementation on the regulation of markers related to T1D. Experimental mice were randomly assigned into five groups, non-STZ + V, STZ + V, STZ + SD1, STZ + SD11, and STZ + SDM (mixture of SD1 and SD11), and physiological data were measured every week. Blood and pancreas samples were collected at 4- and 8-weeks. Our results indicate that supplementation with SD1, SD11, or SDM for 8 weeks significantly improved body weights, glycemic levels, glucose tolerance, insulin levels, and lipid profiles. Probiotic administration also preserved islet integrity and increased β-cell mass in STZ-injected mice, as well as prevented infiltration of macrophages, CD4+, and CD8+ T cells into the islets. Significantly, SD1 and SD11 suppressed the levels of IL1-β, TNF-α and IFN-γ and increased IL-10, which is concomitant with the inhibition of cleaved caspase 3, caspase 9, caspase 8, proapoptotic Bax, NF-κBp65, pSTAT1, and iNOS. Additionally, the survival ability of β-cells was mediated by upregulated anti-apoptotic Bcl2. We conclude that SD1 and SD11 attenuate STZ-induced diabetic mice by stabilizing glycemic levels and reducing inflammation, thereby protecting β-cells. Among the probiotic treatment groups, SD11 revealed the best results in almost all parameters, indicating its potential use for alleviating hyperglycemia-associated symptoms.

摘要

益生菌在各个方面提供健康益处,被认为通过平衡肠道微生物组稳态来调节免疫系统,这被称为“微生物-免疫轴”。最近的证据支持,几种乳酸杆菌菌株在 1 型糖尿病(T1D)的动物模型中具有降低血糖和抗炎作用。虽然副干酪乳杆菌 SD1(SD1)和鼠李糖乳杆菌 SD11(SD11)的益生菌通过减少有害细菌种群来发挥人类口腔健康益处,但它们在与低血糖相关特征以及潜在机制相关的临床应用仍然缺乏。在本报告中,我们使用多次低剂量链脲佐菌素(STZ)诱导的糖尿病 BALB/c 小鼠来探索 SD1 和 SD11 补充对 T1D 相关标志物调节的影响。实验小鼠被随机分为五组,非 STZ+V、STZ+V、STZ+SD1、STZ+SD11 和 STZ+SDM(SD1 和 SD11 的混合物),并每周测量生理数据。在 4 周和 8 周时采集血液和胰腺样本。我们的结果表明,8 周补充 SD1、SD11 或 SDM 可显著改善体重、血糖水平、葡萄糖耐量、胰岛素水平和血脂谱。益生菌给药还可保护胰岛完整性并增加 STZ 注射小鼠的β细胞质量,并防止巨噬细胞、CD4+和 CD8+T 细胞浸润胰岛。值得注意的是,SD1 和 SD11 抑制了 IL1-β、TNF-α 和 IFN-γ 的水平,增加了 IL-10,同时抑制了 cleaved caspase 3、caspase 9、caspase 8、促凋亡 Bax、NF-κBp65、pSTAT1 和 iNOS。此外,β细胞的存活能力是通过上调抗凋亡 Bcl2 介导的。我们得出结论,SD1 和 SD11 通过稳定血糖水平和减少炎症来减轻 STZ 诱导的糖尿病小鼠,从而保护β细胞。在益生菌治疗组中,SD11 在几乎所有参数中都显示出最佳结果,表明其在缓解与高血糖相关的症状方面具有潜力。

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