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通过调节四氧嘧啶诱导的糖尿病大鼠胰岛中的肠道微生物群结构和β细胞再生来研究乳酸杆菌菌株的抗糖尿病潜力

Anti-Diabetic Potentials of Lactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats.

作者信息

Kumar Manoj, Muthurayar Tharmar, Karthika Sukumaran, Gayathri Santhalingam, Varalakshmi Perumal, Ashokkumar Balasubramaniem

机构信息

Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India.

Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, India.

出版信息

Probiotics Antimicrob Proteins. 2025 Jun;17(3):1096-1116. doi: 10.1007/s12602-024-10221-7. Epub 2024 Feb 8.

DOI:10.1007/s12602-024-10221-7
PMID:38329697
Abstract

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90 days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (40%), AngII (30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

摘要

糖尿病是一种最常见的葡萄糖代谢内分泌紊乱疾病,已成为一种全球流行病,并随着社会经济负担的增加对公共卫生构成严重威胁。糖尿病发病率的不断上升与生活方式和饮食习惯的改变相关,这些改变会导致肠道微生物群失调和β细胞损伤,而含有益生菌的饮食干预措施可以解决这些问题。因此,寻找具有抗糖尿病、抗晚期糖基化终末产物(anti-AGE)和抗血管紧张素转换酶(anti-ACE)潜力的人类源益生菌,对于有效管理糖尿病及其相关并发症重新引起了人们的兴趣。本研究使用四氧嘧啶(AXN)诱导的糖尿病大鼠模型,单独研究潜在益生菌干酪乳杆菌MKU1、戊糖片球菌MKU3和植物乳杆菌MKU7给药对与糖尿病发病机制相关的生理化学参数的影响。将实验动物随机分为六组,即正常对照组(NCG)、糖尿病对照组(DCG)、二甲双胍组(DGM)、MKU1组(DGP1)、MKU3组(DGP2)和MKU7组(DGP3),并测量直至90天的血清葡萄糖、胰岛素、血管紧张素II(AngII)、血管紧张素转换酶(ACE)、糖化血红蛋白(HbA1c)和肿瘤坏死因子-α(TNF-α)水平等生化数据。我们的结果表明,口服MKU1、MKU3或MKU7可显著提高血清胰岛素水平、血糖控制水平、葡萄糖耐量和体重。此外,在经乳酸杆菌处理的糖尿病大鼠中,通过保持胰岛完整性增加了β细胞量,而肿瘤坏死因子-α(约40%)、血管紧张素II(约30%)和血管紧张素转换酶水平(约50%)受到强烈抑制,并大量增加了分泌型免疫球蛋白A(sIgA)的产生(5.8倍)。此外,给予乳酸杆菌对肠道微生物群有积极影响,乳酸杆菌属以及有益的单形拟杆菌和脆弱拟杆菌的丰度显著增加,而致病性普通变形杆菌和狄氏副拟杆菌减少。在益生菌治疗组中,戊糖片球菌MKU3在几乎所有参数上表现出色,表明其在减轻糖尿病相关并发症方面的潜在用途。

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Probiotics of Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 attenuate inflammation and β-cell death in streptozotocin-induced type 1 diabetic mice.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。
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RAGE signaling regulates the progression of diabetic complications.
晚期糖基化终末产物受体信号传导调节糖尿病并发症的进展。
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