Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury.
Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury.
复制标题
丁酸钠治疗的 db/db 小鼠粪便移植可减轻缺血性中风损伤
DOI：
10.1128/spectrum.00042-21
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发表时间：
2021-10-31
影响因子：
3.7
通讯作者：
Yin J
中科院分区：
文献类型：
--
作者：
Wang H;Song W;Wu Q;Gao X;Li J;Tan C;Zhou H;Zhu J;He Y;Yin J
2型糖尿病（T2D）并发症加重急性缺血性卒中（AIS）脑梗死。由于产生丁酸盐的细菌在T2D中减少，并且有报道称丁酸盐与AIS患者脑损伤的减轻有关，我们假设给予丁酸盐可以改善AIS患者T2D相关的脑梗死加重。因此，我们首先验证了合并T2D的中国AIS患者粪便中产生丁酸菌和丁酸盐的水平明显低于没有T2D的AIS患者。然后，我们对接受丁酸钠（SB）或氯化钠（NaCl）的T2D小鼠进行了为期4周的干预，发现SB改善了糖尿病表型，改变了肠道微生物群，并改善了脑卒中后的脑损伤。将经SB或NaCl处理的T2D小鼠的粪便样本移植到经抗生素处理的C57BL/6小鼠体内。移植2周后，检测受体小鼠肠道菌群分布和丁酸盐水平，然后对受体小鼠进行缺血性脑卒中治疗。接受sb处理小鼠肠道菌群的中风小鼠脑梗死体积小于接受nacl处理小鼠肠道菌群的小鼠。这种保护还与肠道屏障功能的改善、血清脂多糖（LPS）、脂多糖结合蛋白（LBP）和促炎细胞因子水平的降低以及血脑屏障的改善有关。缺血性卒中是全球主要的健康负担，众所周知，T2D是缺血性卒中后加重脑损伤的合并症。然而，T2D加重脑卒中损伤的潜在机制尚未完全阐明。大量证据表明，肠道微生物群的组成影响中风的结果。我们的研究结果表明，T2D的肠道微生物群加重了缺血性脑卒中后的脑损伤，并可能被SB修饰，以提供对脑卒中损伤的神经保护。这些发现表明补充SB是T2D合并缺血性脑卒中患者的潜在治疗策略。
The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.