Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats.

Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats.
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DOI:
10.1080/19490976.2022.2136467
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发表时间:
2022-01
期刊:
影响因子:
12.2
通讯作者:
--
中科院分区:
医学2区
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1型糖尿病发病率的增加与低纤维、高面筋的西方饮食和其他与生态失调有关的环境因素的出现相吻合。由于补充植物乳杆菌299 v(Lp 299 v)可改善肠道屏障功能并减少全身炎症,因此我们研究了其在提供正常谷物饮食(ND)或无麸质水解酪蛋白饮食(HCD)的自发性糖尿病DRlyp/lyp大鼠中的作用。所有提供ND的大鼠均发生糖尿病(62.5±7.7天); ND与Lp 299 v联合使用并未改善存活率。糖尿病被HCD延迟(72.2±9.4天,p = .01),并且被HCD+ Lp 299 v进一步延迟(84.9±14.3天,p < .001)。HCD+ Lp 299 v幼仔表现出血浆丙酸盐和丁酸盐水平升高,这与富集的粪便双歧杆菌科和梭菌目分类群相关。40日龄时的胰岛转录组学和组织学分析显示,喂食HCD的大鼠表达自噬特征,而喂食HCD+ Lp 299 v的大鼠表达ER相关蛋白降解(ERAD)和抗氧化防御途径,包括Nrf 2。将胰岛素瘤细胞暴露于丙酸盐和丁酸盐促进了抗氧化防御反应,但没有概括HCD+ Lp 299 v胰岛ERAD转录组学特征。在这里,饮食和微生物群都影响糖尿病易感性。此外,Lp 299 v补充剂调节β细胞中的抗氧化防御和ER应激反应,可能提供新的治疗方向以阻止糖尿病进展并保护胰岛素分泌。
The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since Lactiplantibacillus plantarum 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DRlyp/lyp rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.5±7.7 days); combining ND with Lp299v did not improve survival. Diabetes was delayed by HCD (72.2±9.4 days, p = .01) and further delayed by HCD+Lp299v (84.9±14.3 days, p < .001). HCD+Lp299v pups exhibited increased plasma propionate and butyrate levels, which correlated with enriched fecal Bifidobacteriaceae and Clostridiales taxa. Islet transcriptomic and histologic analyses at 40-days of age revealed that rats fed HCD expressed an autophagy profile, while those provided HCD+Lp299v expressed ER-associated protein degradation (ERAD) and antioxidative defense pathways, including Nrf2. Exposing insulinoma cells to propionate and butyrate promoted the antioxidative defense response but did not recapitulate the HCD+Lp299v islet ERAD transcriptomic profile. Here, both diet and microbiota influenced diabetes susceptibility. Moreover, Lp299v supplement modulated antioxidative defense and ER stress responses in β-cells, potentially offering a new therapeutic direction to thwart diabetes progression and preserve insulin secretion.
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