Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice.
Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice.
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肠道微生物区系中产醋酸菌的枯竭通过肠道-大脑神经机制促进糖尿病小鼠的认知障碍。
DOI：
10.1186/s40168-021-01088-9
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发表时间：
2021-06-25
期刊：
影响因子：
15.5
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Zheng H;Xu P;Jiang Q;Xu Q;Zheng Y;Yan J;Ji H;Ning J;Zhang X;Li C;Zhang L;Li Y;Li X;Song W;Gao H
据报道，肠道微生物区系的改良可以降低1型糖尿病(T1D)的发病率。我们假设肠道微生物区系的变化也可能对T1D的认知功能产生影响。在这里，我们使用不可吸收的抗生素万古霉素来修饰链脲佐菌素(STZ)诱导的T1D小鼠的肠道微生物区系，并研究微生物变化对T1D小鼠认知能力的影响及其潜在的肠脑神经机制。我们发现，万古霉素暴露扰乱了肠道微生物组，改变了宿主的代谢表型，并促进了T1D小鼠的认知障碍。由于产醋酸菌的枯竭而导致的长期醋酸盐缺乏导致海马区突触素(SYP)的减少以及学习和记忆障碍。外源性醋酸盐补充或粪便微生物区系移植可恢复万古霉素处理的T1D小鼠海马区SYP水平，这种影响可被迷走神经抑制或切断迷走神经减弱。我们的结果证明了微生物区系代谢物醋酸盐在认知功能中的保护作用，并表明长期醋酸盐缺乏是认知能力下降的一个风险因素。视频摘要在线版本包含可在10.1186/s40168021-01088-9上查阅的补充材料。
Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline. Video Abstract The online version contains supplementary material available at 10.1186/s40168-021-01088-9.
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影响因子：
16.6
作者：
Antunes, Krist Helen;Fachi, Jose Luis;Duarte de Souza, Ana Paula
通讯作者：
Duarte de Souza, Ana Paula
影响因子：
3
作者：
Awad, Anna;Lundqvist, Robert;Eliasson, Mats
通讯作者：
Eliasson, Mats
DOI：
10.1007/978-1-4939-8728-3_11
发表时间：
2018-01-01
期刊：
MICROBIOME ANALYSIS
影响因子：
--
作者：
Douglas, Gavin M.;Beiko, Robert G.;Langille, Morgan G. I.
通讯作者：
Langille, Morgan G. I.
DOI：
10.1126/science.1209236
发表时间：
2011-11-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ho VM;Lee JA;Martin KC
通讯作者：
Martin KC
影响因子：
2.7
作者：
Alvarez, Edgardo O.;Beauquis, Juan;Saravia, Flavia
通讯作者：
Saravia, Flavia