Mani Sridhar, Boelsterli Urs A, Redinbo Matthew R
Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, New York 10461.
Annu Rev Pharmacol Toxicol. 2014;54:559-80. doi: 10.1146/annurev-pharmtox-011613-140007. Epub 2013 Oct 23.
The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.
早在1885年，人们就注意到人类胃肠道中的细菌发挥着共生作用，这远在我们开始使用抗生素治疗微生物感染之前。然而，即使是人类使用的首批抗菌化合物——磺胺类药物，微生物也被认为在这些治疗药物的生物转化中起着关键作用。因此，微生物群在生理学和人类健康管理中所起的作用早已为人所知。始于21世纪初对胃肠道共生细菌的详细研究以及2012年完成的人类微生物组计划的第一阶段，开启了一个令人兴奋的精细化时期，涉及哺乳动物与微生物交流轴的生态学、遗传学和化学。在这里，我们回顾了胃肠道共生细菌与几种哺乳动物系统之间起作用的生化途径的各个方面，包括影响炎症、免疫学、新陈代谢和神经生物学的局部上皮和非局部反应。最后，我们讨论了如何调节治疗化合物（如抗癌药或非甾体抗炎药）的微生物生物转化，以降低毒性并可能提高治疗效果。
