缺失HDAC6改变小鼠肠道菌群并加剧肥胖
创作:aluba 审核:aluba 2018年08月18日
  • 野生型小鼠与组蛋白去乙酰化酶-6(HDAC6)缺陷小鼠产生的后代在围产期使用青霉素处理,通过扰乱菌群诱导体重增加;
  • 雄性小鼠中,HDAC6缺陷未表现出对肥胖的保护作用,表现出了加速的体重增加;
  • 暴露于抗生素的HDAC6缺陷小鼠CD4及CD8 T细胞活化增强,同时Treg细胞的功能也增强;
  • 在高脂饮食下,HDAC6缺陷小鼠肠道菌群中的S24-7科及乳杆菌属缺失,而拟杆菌属及Parabacteroides富集,这些菌群的变化与肥胖相关。
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aluba
抗生素处理可通过去除可产生组蛋白去乙酰化酶抑制剂的菌群,影响体重。FASEB Journal发表的一项最新研究,发现缺失了组蛋白去乙酰化酶-6的小鼠,并未表现出对肥胖的抗性,而是表现出体重增加的加速。HDAC6缺陷可能导致CD4及CD8 T细胞活化增强,并导致肠道菌群失调,从而促进肥胖。
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FASEB Journal [IF:5.834]

Loss of HDAC6 alters gut microbiota and worsens obesity

缺失HDAC6改变肠道菌群并加剧肥胖

10.1096/fj.201701586R

2018-08-13, Article

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Alterations in gut microbiota are known to affect intestinal inflammation and obesity. Antibiotic treatment can affect weight gain by elimination of histone deacetylase (HDAC) inhibitor-producing microbes, which are anti-inflammatory by augmenting regulatory T (T) cells. We asked whether mice that lack HDAC6 and have potent suppressive T cells are protected from microbiota-induced accelerated weight gain. We crossed wild-type and HDAC6-deficient mice and subjected the offspring to perinatal penicillin, inducing weight gain via microbiota disturbance. We observed that male HDAC6-deficient mice were not protected and developed profoundly accelerated weight gain. The antibiotic-exposed HDAC6-deficient mice showed a mixed immune phenotype with increased CD4 and CD8 T-cell activation yet maintained the enhanced T cell-suppressive function phenotype characteristic of HDAC6-deficient mice. 16S rRNA sequencing of mouse fecal samples reveals that their microbiota diverged with time, with HDAC6 deletion altering microbiome composition. On a high-fat diet, HDAC6-deficient mice were depleted in representatives of the S24-7 family and Lactobacillus but enriched with Bacteroides and Parabacteroides; these changes are associated with obesity. Our findings further our understanding of the influence of HDACs on microbiome composition and are important for the development of HDAC6 inhibitors in the treatment of human diseases.-Lieber, A. D., Beier, U. H., Xiao, H., Wilkins, B. J., Jiao, J., Li, X. S., Schugar, R. C., Strauch, C. M., Wang, Z., Brown, J. M., Hazen, S. L., Bokulich, N. A., Ruggles, K. V., Akimova, T., Hancock, W. W., Blaser, M. J. Loss of HDAC6 alters gut microbiota and worsens obesity.

First Authors:
Arnon D Lieber

Correspondence Authors:
Martin J Blaser

All Authors:
Arnon D Lieber,Ulf H Beier,Haiyan Xiao,Benjamin J Wilkins,Jing Jiao,Xinmin S Li,Rebecca C Schugar,Christopher M Strauch,Zeneng Wang,J Mark Brown,Stanley L Hazen,Nicholas A Bokulich,Kelly V Ruggles,Tatiana Akimova,Wayne W Hancock,Martin J Blaser

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