小柯机器人

定向改造小鼠肠道微生物群可抑制动脉粥样硬化的发生
2020-06-17 18:26

美国斯克里普斯研究学院M. Reza Ghadiri和 Luke J. Leman研究组发现,小鼠肠道微生物的定向改造抑制了动脉粥样硬化的发展。该研究于2020年6月15日发表于《自然-生物技术》杂志。

研究人员设计了小鼠肠道微生物组的体外筛选方案,以发现可以选择性修饰细菌生长的分子。该方法鉴定发现了环状D、L-α-肽,其将西方饮食(WD)人群的肠道微生物组重塑为低脂饮食微生物组状态。在WD喂养的LDLr-/-小鼠中每天口服给予该肽可降低血浆总胆固醇水平和动脉粥样硬化斑块。

用抗生素清除微生物组则消除了这些影响。肽处理可使微生物组的转录组重编程,抑制促炎细胞因子(包括白介素-6、肿瘤坏死因子-α和白介素-1β)的产生,短链脂肪酸和胆汁酸水平的重新平衡,改善肠屏障的完整性并增加肠道T调节细胞。定向化学操作为揭示肠道微生物组的化学生物学特性提供了额外的工具,并可能促进针对微生物组治疗方法的发展。

据悉,肠道微生物组是具有延展性的微生物群落,可以响应包括饮食在内的各种因素而重塑,并会助推动脉粥样硬化等多种慢性疾病的发展。

附:英文原文

Title: Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis

Author: Poshen B. Chen, Audrey S. Black, Adam L. Sobel, Yannan Zhao, Purba Mukherjee, Bhuvan Molparia, Nina E. Moore, German R. Aleman Muench, Jiejun Wu, Weixuan Chen, Antonio F. M. Pinto, Bruce E. Maryanoff, Alan Saghatelian, Pejman Soroosh, Ali Torkamani, Luke J. Leman, M. Reza Ghadiri

Issue&Volume: 2020-06-15

Abstract: The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr/ mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.

DOI: 10.1038/s41587-020-0549-5

Source: https://www.nature.com/articles/s41587-020-0549-5

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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