肠道菌群可影响心肌梗死结局

创作:mildbreeze 审核:mildbreeze 10月11日
口服抗生素(ABX)减少肠道菌群后,小鼠心肌梗死(MI)死亡率随ABX用量增多而显著上升;
缺乏肠道菌群,使小鼠短链脂肪酸(SCFA)水平和髓系细胞比例降低,MI后围梗死区CX3CR1+单核细胞浸润减少,致MI后心脏修复受损;
粪菌移植、单核细胞移植、补充SCFA,均显著改善ABX小鼠MI后的生理和生存情况;
MI引起肠道菌群改变,乳杆菌属减少,给ABX小鼠在MI前补充混合乳杆菌,可促进丙酸生成、恢复髓系细胞比例,有心血管保护作用。
延伸阅读
Circulation [IF:18.88]

Loss of Gut Microbiota Alters Immune System Composition and Cripples Post-Infarction Cardiac Repair

缺乏肠道菌群改变了免疫系统组成并削弱梗死后心脏修复

10-08, Article, 10.1161/CIRCULATIONAHA.118.035235more

Abstract:
Background : The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.
Methods: To investigate the effects of gut microbiota on cardiac repair after myocardial infarction (MI), C57BL/6J mice were treated with antibiotics 7 days prior to MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S ribosomal DNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by HPLC. Fecal reconstitution, transplantation of monocytes, dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.
Results: Antibiotic-treated mice (ABX mice) displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells, and SCFA, more specifically acetate, butyrate and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved following fecal reconstitution, transplantation of monocytes or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community, such as a reduction in Lactobacillus. Supplementing ABX mice with a Lactobacillus probiotic prior to MI restored myeloid cell proportions, yielded cardioprotective effects and shifted the balance of SCFAs towards propionate.
Conclusions: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI, and indeed human health and disease as a whole.

First Authors:
Tony WH Tang,Hung-Chih Chen

Correspondence Authors:
Patrick CH Hsieh

All Authors:
Tony WH Tang,Hung-Chih Chen,Chen-Yun Chen,Christopher YT Yen,Chen-Ju Lin,Ray Putra Prajnamitra,Li-Lun Chen,Shu-Chian Ruan,Jen-Hao Lin,Po-Ju Lin,Hsueh-Han Lu,Chiung Wen Kuo,Cindy M Chang,Alexander D Hall,Eugenio I Vivas,Jr-Wen Shui,Peilin Chen,Timothy A Hacker,Federico E Rey,Timothy J Kamp,Patrick CH Hsieh