Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance.

Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance.
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DOI:
10.1080/19490976.2020.1814107
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发表时间:
2020-11-09
期刊:
影响因子:
12.2
通讯作者:
Bryan RM
Bryan RM
中科院分区:
医学2区
文献类型:
--
作者:
Lee J;Venna VR;Durgan DJ;Shi H;Hudobenko J;Putluri N;Petrosino J;McCullough LD;Bryan RM

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衰老与认知能力下降和肠道中短链脂肪酸(SCFA)浓度降低有关。SCFA的重要性在于它们对肠道和其他器官具有保护作用。我们测试了一个假设,即老化的肠道微生物组本身就足以减少宿主中的SCFA并产生认知能力下降。在约3月龄时开始将来自老龄(18-20个月)或年轻(2-3个月)雄性C57 BL/6小鼠的粪便移植管饲(FTG)注入无菌雄性C57 BL/6小鼠(每组N = 11)。在研究期间收集粪便样品并进行行为测试。通过对细菌16 S核糖体RNA基因进行测序来测量粪便样品中的细菌群落结构和相对丰度。在FTG后30、60和90 d,具有老年和年轻微生物组的小鼠在细菌β多样性方面表现出明显的差异(每个P = 0.001)。在具有老化微生物组的小鼠中,粪便SCFA、乙酸盐、丙酸盐和丁酸盐(微生物组效应,每种P <0.01)减少。在初始FTG后的3个月内,具有老化微生物组的小鼠表现出抑郁样行为、短期记忆受损和空间记忆受损,分别通过尾部悬挂(P = .008)、新物体识别(P < .001)和巴恩斯迷宫(P = .030)测试进行评估。我们的结论是,单独的老化微生物组足以减少宿主中的SCFA并产生认知能力下降。
Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18–20 months) or young (2–3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S ribosomal RNA gene. Mice with aged and young microbiomes showed clear differences in bacterial β diversity at 30, 60, and 90 d (P = .001 for each) after FTGs. The fecal SCFAs, acetate, propionate, and butyrate (microbiome effect, P < .01 for each) were decreased in mice with an aged microbiome. Mice with an aged microbiome demonstrated depressive-like behavior, impaired short-term memory, and impaired spatial memory over the 3 months following the initial FTG as assessed by the tail suspension (P = .008), the novel object recognition (P < .001), and the Barnes Maze (P = .030) tests, respectively. We conclude that an aged microbiome alone is sufficient to decrease SCFAs in the host and to produce cognitive decline.
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