Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis.
Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis.
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肠道微生物群通过抑制糖酵解介导饮食限制小鼠的淋巴细胞生成抑制
DOI：
10.1080/19490976.2022.2117509
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发表时间：
2022-01
期刊：
影响因子：
12.2
通讯作者：
Tang, Duozhuang
中科院分区：
文献类型：
--
作者：
Tao, Si;Wang, Yiting;Yu, Chenghui;Qiu, Rongrong;Jiang, Yanjun;Jia, Jie;Tao, Zhendong;Zhang, Liu;Zou, Bing;Tang, Duozhuang
饮食限制（DR）是延长健康寿命的最有力的干预措施之一，并且仍然处于抗衰老干预研究的前沿，尽管在啮齿动物和灵长类动物中对其寿命的影响显示出相互矛盾的结果。DR对淋巴谱系的严重抑制作用仍然是其主要的负面影响之一，这降低了其对生物体健康的总体有益作用。然而，DR如何抑制淋巴系统的潜在机制仍有待探索。在这里，我们表明，肠道菌群的抗生素消融显着挽救了DR淋巴细胞生成的抑制。有趣的是，淋巴细胞中的糖酵解在DR小鼠中显着下调，糖酵解的药理学抑制逆转了这种救援作用的淋巴细胞生成在DR小鼠与消融肠道菌群。此外，DR显着重建肠道微生物群，显著增加丁酸盐生产细菌类群和But的表达，But是参与丁酸盐合成的关键基因。此外，补充丁酸盐喂养AL小鼠抑制淋巴细胞的糖酵解，并模仿AL小鼠淋巴细胞生成的抑制。总之，我们的研究表明，肠道微生物群通过在DR条件下下调糖酵解介导对淋巴细胞生成的抑制，这与丁酸合成增加有关。我们的研究发现了一种可能用于改善DR对淋巴细胞生成的负面影响的候选物，因此可能对DR的更广泛应用和促进健康老龄化具有重要意义。
Dietary restriction (DR) is one of the most robust interventions shown to extend health-span and remains on the forefront of anti-aging intervention studies, though conflicting results have been shown on its effect on lifespan both in rodents and primates. The severe inhibitory effects on the lymphoid lineage by DR remains one of its major negative downsides which reduces its overall beneficial effects on organismal health. Yet, the underlying mechanism of how DR suppresses the lymphoid system remains to be explored. Here, we show that antibiotic ablation of gut microbiota significantly rescued the inhibition of lymphopoiesis by DR. Interestingly, glycolysis in lymphocytes was significantly down-regulated in DR mice and pharmacological inhibition of glycolysis reverted this rescue effect of lymphopoiesis in DR mice with ablated gut microbiota. Furthermore, DR remarkably reconstructed gut microbiota with a significant increase in butyrate-producing bacterial taxa and in expression of But, a key gene involved in butyrate synthesis. Moreover, supplemental butyrate feeding in AL mice suppressed glycolysis in lymphoid cells and mimicked the inhibition of lymphopoiesis in AL mice. Together, our study reveals that gut microbiota mediates the inhibition on lymphopoiesis via down-regulation of glycolysis under DR conditions, which is associated with increased butyrate-synthesis. Our study uncovered a candidate that could potentially be targeted for ameliorating the negative effects of DR on lymphopoiesis, and therefore may have important implications for the wider application of DR and promoting healthy aging.
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DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
肠道微生物群形成短链脂肪酸及其对人代谢的影响。
影响因子：
12.2
作者：
Morrison DJ;Preston T
通讯作者：
Preston T
影响因子：
64.8
作者：
Mattison, Julie A.;Roth, George S.;Beasley, T. Mark;Tilmont, Edward M.;Handy, April M.;Herbert, Richard L.;Longo, Dan L.;Allison, David B.;Young, Jennifer E.;Bryant, Mark;Barnard, Dennis;Ward, Walter F.;Qi, Wenbo;Ingram, Donald K.;de Cabo, Rafael
通讯作者：
de Cabo, Rafael
影响因子：
7.8
作者：
Harper, James M.;Leathers, Charles W.;Austad, Steven N.
通讯作者：
Austad, Steven N.
影响因子：
13.8
作者：
Longo VD;Fontana L
通讯作者：
Fontana L