人体共生微生物的研究简史!值得收藏
在很多人的感知中,人类相关微生物群(Human Assiociated Microbiota)可能还只是一个新生的研究领域。但实际上,人类对这一生物类群的描述可以追溯到 1670 年代至 1680 年代。当时,安东尼·范·列文虎克研发了一种新的手工显微镜,并正兴致盎然地观察一个前所未见的微观生物世界。到如今,我们对人类相关微生物群的研究已经取得了长足的进步。那么在此过程中,是哪些关键进展推动了我们从观察单个细胞转向对复杂微生物群落的研究呢?就让我们跟随《Nature 里程碑》系列 ,探索一番该领域的基础性突破和进展吧。
(原文链接:https://www.nature.com/immersive/d42859-019-00041-z/index.html)
1944:体外培养厌氧菌 [1]
1944 年,在研究牛瘤胃中负责降解纤维素的微生物时,Robert. E. Hungate 革命性地使用滚管法成功培养了厌氧菌——纤维梭菌。经过不断完善,该方法已成为厌氧微生物分离培养的经典方法,也让人类首次分离出人类相关厌氧菌(human-associated anaerobes)。
[1] Culturing anaerobesn
(https://www.nature.com/articles/d42859-019-00007-1)
1958:粪便微生物群移植治疗感染 [2]
[2] Faecal microbiota transplantation for Clostridioides difficile infection
(https://www.nature.com/articles/d42859-019-00008-01)
1965:肠道微生物移植模型 [3]
[3] Gut microbiota transfer experiments in germ-free animals
(https://www.nature.com/articles/d42859-019-00009-z)
1972:微生物群影响宿主药物代谢 [4]
Peppercorn 和 Goldman 证明,抗炎药——水杨基磺胺吡啶——可以在野生大鼠以及接受人类肠道细菌移植的大鼠体内被降解,但在无菌大鼠体内则不会被降解,表明了肠道微生物群在药物转化方面的作用。此后越来越多的研究证实,微生物群在药物代谢中的作用不限于肠道微生物,对药物代谢、灭活、疗效和毒副作用等方面都有重要影响。
[4] Peppercorn, M. A. & Goldman, P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J. Pharmacol. Exp. Ther. 181, 555–562 (1972).
1981:婴儿共生微生物的演替 [5]
[5] Microbiota succession in early life
(https://www.nature.com/articles/d42859-019-00010-6)
视频:生死相依的微生物 [6]
[6] The microbes that live with us from cradle to grave
1996:基于序列鉴定菌群 [7]
[7] Sequence-based identification of human-associated microbiota
(https://www.nature.com/articles/d42859-019-00011-5)
1998:菌群的稳定性与独特性 [8]
[8] Stability and individuality of adult microbiota
(https://www.nature.com/articles/d42859-019-00012-4)
2003:细菌之外的共生微生物 [9]
[9] Beyond bacteria: studies of other host-associated microorganisms
(https://www.nature.com/articles/d42859-019-00013-3)
2004:微生物群对粘膜免疫的调节 [10]
2004年的两项研究,揭示了免疫系统如何感知微生物群,以及在正常条件下,细菌如何调节免疫系统的发育。这些发现为理解共生微生物与免疫反应的关系开辟了新的视角:它们之间并不是简单的宿主防御关系,而是一种共生的生理过程。
[10] Regulation of mucosal immunity by the microbiota
(https://www.nature.com/articles/d42859-019-00014-2)
2005:养好肠道菌群的重要性[11]
[11] The importance of feeding your microbiota
(https://www.nature.com/articles/d42859-019-00007-1)
2006:肠道菌群移植的治疗潜力 [12]
[12] Transfer of host phenotypes through microbiota transplantation
(https://www.nature.com/articles/d42859-019-00016-0)
2006:饮食通过肠道菌群影响健康 [13]
[13] Impact of diet–microbiota interactions on human metabolism
(https://www.nature.com/articles/d42859-019-00017-z)
2007:定植抵抗的机制 [14]
[14] Mechanisms of colonization resistance
(https://www.nature.com/articles/d42859-019-00018-y)
2007:肠道菌群进入组学时代 [15]
[15] Klaassens, E. S., de Vos, W. M. & Vaughan, E. E. Metaproteomics approach to study the functionality of the microbiota in the human infant gastrointestinal tract. Appl. Environ. Microbiol. 73, 1388–1392 (2007).
2008:抗生素破坏肠道菌群 [16]
[16] Antibiotics alter the gut microbiome and host health.
(https://www.nature.com/articles/d42859-019-00019-x)
2010:微生物测序数据分析工具 [17]
[17] Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 7, 335–336 (2010).
2011:群体规模的菌群分析 [18]
[18] Microbiome analyses in large human populations
(https://www.nature.com/articles/d42859-019-00020-4)
2012:微生物组-肠-脑轴 [19]
[19] The microbiota–gut–brain axis
(https://www.nature.com/articles/d42859-019-00021-3)
2012:新培养方式扩大可培养菌群[20]
[20] Modern culturing efforts expand the culturable microbiota
(Goodman, A. L. et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc. Natl Acad. Sci. USA 108, 6252–6257 (2011).)
2012:全球的人类微生物组 [21]
[21] Global human microbiome
(Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012))
2013:微生物短链脂肪酸诱导Treg [22]
[22] Microbially-produced short-chain fatty acids induce regulatory T cell production
(Smith, P.M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013)
Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013)
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013))
2014:人类微生物群产生的抗生素 [23]
[23] Production of antibiotics by the human microbiota
(Donia, M. S. et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 158, 1402–1414 (2014))
2015:宿主靶向药物影响微生物群 [24]
[24] Host-targeted drugs affect microbiota populations
(Tsuda A et al. Influence of proton-pump inhibitors on the luminal microbiota in the gastrointestinal tract. Clin. Transl. Gastroenterol. 6, e89 (2015)
Freedberg, D. E. et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: a crossover trial. Gastroenterology 149, 883–885 (2015)
Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262–266 (2015).)
2018:人类微生物群影响癌症治疗 [25]
[25] Human microbiota affects response to cancer therapy
(Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018)
Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients Science 359, 97–103 (2018)
Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018))
2019:宏基因组组装发现新特征 [26]
[26] Metagenome-assembled genomes provide unprecedented characterization of human-associated microbiota
(Pasolli, E. et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell 176, 649–662 (2019)
Almeida, A. et al. A new genomic blueprint of the human gut microbiota. Nature 568, 499–504 (2019)
Nayfach, S. et al. New insights from uncultivated genomes of the global human gut microbiome. Nature 568, 505–510 (2019))
参考资料:https://www.nature.com/immersive/d42859-019-00041-z/index.html