Butyrate Ameliorates Antibiotic-Driven Type 1 Diabetes in the Female Offspring of Nonobese Diabetic Mice.
Butyrate Ameliorates Antibiotic-Driven Type 1 Diabetes in the Female Offspring of Nonobese Diabetic Mice.
复制标题
丁酸盐可改善非肥胖糖尿病小鼠雌性后代由抗生素引起的 1 型糖尿病。
DOI：
10.1021/acs.jafc.9b07701
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发表时间：
2020
影响因子：
6.1
通讯作者：
Pan Li-Long
中科院分区：
文献类型：
--
作者：
Jia Lingling;Cao Minkai;Chen Hao;Zhang Ming;Dong Xiaoliang;Ren Zhengnan;Sun Jia;Pan Li-Long
母体肠道生物失调会影响子代免疫系统的发育。我们先前的研究表明，微生物代谢物丁酸盐直接形成胰腺免疫耐受，并抑制1型糖尿病(T1D)的进展。因此，母体丁酸干预可能会保护他们的后代免受母体肠道生物失调加速的T1D的影响。为了测试这一点，在怀孕和哺乳期间(口服万古霉素用于诱导母体肠道生物失调)，在妊娠和哺乳期间，在添加或不添加丁酸盐的饮食的情况下，在饮用水中使用万古霉素对非肥胖糖尿病(NOD)小鼠进行治疗。出生3周后，检测T1D相关的先天免疫细胞和获得性免疫细胞，以探讨丁酸盐对万古霉素所致的胰腺免疫紊乱的影响。结果表明，丁酸盐可抑制母体促炎症细胞因子(干扰素γ和白介素1β)的分泌和母体干扰素γ+T细胞(细胞毒性T淋巴细胞1细胞和辅助性T细胞1)在雌性子代胰腺中的募集，从而抑制T1D的发育。其保护作用可能与丁酸抑制胰腺树突状细胞(DC)的活化有关。因此，我们的数据表明，母体肠道生物失调可以通过丁酸盐抑制的T细胞和DC相关机制来加剧雌性后代胰腺导向的自身免疫。
Maternal gut dysbiosis affects the development of the offspring immune system. Our previous study has indicated that microbial metabolite butyrate directly shapes pancreatic immune tolerance and dampens type 1 diabetes (T1D) progression. Therefore, maternal butyrate intervention may protect their offspring from maternal gut dysbiosis-accelerated T1D. To test this, pregnant nonobese diabetic (NOD) mice were treated with vancomycin in drinking water with or without a butyrate-supplemented diet during gestation and nursing (oral vancomycin is used to induce maternal gut dysbiosis). Three weeks after delivery, T1D-associated innate and adaptive immune cells were detected to investigate the effects of butyrate on the vancomycin-exacerbated pancreatic immune disorder in dams and pups. The results showed that butyrate inhibited maternal vancomycin-exacerbated secretion of proinflammation cytokines (interferon γ and interleukin-1β) and maternal vancomycin-exacerbated recruitment of interferon γ+T cells (cytotoxic T lymphocytes 1 cells and T helper type 1 cells) in the pancreas of the female offspring, thus dampening T1D development. The protection may be due to butyrate inhibiting the activation of pancreatic dendritic cells (DCs). Our data thus demonstrate that maternal gut dysbiosis can exacerbate pancreatic-directed autoimmunity in the female offspring through T cell- and DC-associated mechanisms that are inhibited by butyrate.