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通过免疫调节益生菌改善非肥胖糖尿病(NOD)小鼠的自身免疫性糖尿病

Amelioration of Autoimmune Diabetes of NOD Mice by Immunomodulating Probiotics.

作者信息

Kim Tae Kang, Lee June-Chul, Im Sin-Hyeog, Lee Myung-Shik

机构信息

Department of Internal Medicine, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, South Korea.

出版信息

Front Immunol. 2020 Sep 3;11:1832. doi: 10.3389/fimmu.2020.01832. eCollection 2020.

DOI:10.3389/fimmu.2020.01832
PMID:33013834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7496355/
Abstract

Type 1 autoimmune diabetes is an autoimmune disease characterized by specific destruction of pancreatic β-cells producing insulin. Recent studies have shown that gut microbiota and immunity are closely linked to systemic immunity, affecting the balance between pro-inflammatory and regulatory immune responses. Altered gut microbiota may be causally related to the development of immune-mediated diseases, and probiotics have been suggested to have modulatory effects on inflammatory diseases and immune disorders. We studied whether a probiotic combination that has immunomodulatory effects on several inflammatory diseases can reduce the incidence of diabetes in non-obese diabetic (NOD) mice, a classical animal model of human T1D. When Immune Regulation and Tolerance 5 (IRT5), a probiotic combination comprising , and , was administered 6 times a week for 36 weeks to NOD mice, beginning at 4 weeks of age, the incidence of diabetes was significantly reduced. Insulitis score was also significantly reduced, and β-cell mass was conversely increased by IRT5 administration. IRT5 administration significantly reduced gut permeability in NOD mice. The proportion of total regulatory T cells was not changed by IRT5 administration; however, the proportion of CCR9 regulatory T (Treg) cells expressing gut-homing receptor was significantly increased in pancreatic lymph nodes (PLNs) and lamina propria of the small intestine (SI-LP). Type 1 T helper (Th1) skewing was reduced in PLNs by IRT5 administration. IRT5 could be a candidate for an effective probiotic combination, which can be safely administered to inhibit or prevent type 1 diabetes (T1D).

摘要

1型自身免疫性糖尿病是一种自身免疫性疾病,其特征是产生胰岛素的胰腺β细胞受到特异性破坏。最近的研究表明,肠道微生物群与免疫密切相关,影响全身免疫,进而影响促炎和调节性免疫反应之间的平衡。肠道微生物群的改变可能与免疫介导疾病的发生有因果关系,并且已有人提出益生菌对炎症性疾病和免疫紊乱具有调节作用。我们研究了一种对多种炎症性疾病具有免疫调节作用的益生菌组合是否可以降低非肥胖糖尿病(NOD)小鼠(人类1型糖尿病的经典动物模型)的糖尿病发病率。当从4周龄开始,每周给NOD小鼠施用6次免疫调节与耐受5(IRT5,一种由[具体成分未给出]组成的益生菌组合),持续36周时,糖尿病发病率显著降低。IRT5给药还显著降低了胰岛炎评分,相反,β细胞量增加。IRT5给药显著降低了NOD小鼠的肠道通透性。IRT5给药并未改变总调节性T细胞的比例;然而,在胰腺淋巴结(PLN)和小肠固有层(SI-LP)中,表达肠道归巢受体的CCR9调节性T(Treg)细胞的比例显著增加。IRT5给药降低了PLN中1型辅助性T(Th1)细胞的偏向性。IRT5可能是一种有效的益生菌组合候选物,可以安全地给药以抑制或预防1型糖尿病(T1D)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/a9f8b900b05f/fimmu-11-01832-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/8214e7078888/fimmu-11-01832-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/215d97fcc410/fimmu-11-01832-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/bac4b3d56a20/fimmu-11-01832-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/a9f8b900b05f/fimmu-11-01832-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/8214e7078888/fimmu-11-01832-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/215d97fcc410/fimmu-11-01832-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/bac4b3d56a20/fimmu-11-01832-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8196/7496355/a9f8b900b05f/fimmu-11-01832-g0004.jpg

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