科学家发现抗生素改变肠道菌群代谢机制

2013-02-02 11:24 · lobu

瓦伦西亚大学科学家研究发现抗生素改变肠道微生物代谢的机制,第一次证实肠道细菌有能力产生某些关键蛋白质,以及在治疗期间其治疗活跃程度会有所不同。

瓦伦西亚大学一项研究显示,抗生素能改变肠道微生物及其代谢模式。研究人员第一次分析了抗生素治疗患者肠道菌群的细菌类型、基因、酶和分子,相关研究结果发布在《Gut》杂志上。人体肠道中生活着亿万个细菌,它们被称为微生物或肠道菌群。根据这项研究,在早期阶段治疗中抗生素会改变人与细菌的共生状态。

研究第一次证实肠道细菌有能力产生某些关键蛋白质,以及在治疗期间其治疗活跃程度会有所不同。具体来说,该项研究表明肠道菌群对铁的吸收能力较弱。研究还表明,肠道菌群的细菌在开始治疗时,很少是活跃的。但在治疗结束后,它们会变得异常活跃,这些细菌能改善肝脏和结肠之间胆汁酸、激素和胆固醇衍生物的产生。

Gut microbiota disturbance during antibiotic therapy: a multi-omic approach

Ana Elena Pérez-Cobas et al.

Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy.

Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated.

Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation.

Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.

文献链接:Gut microbiota disturbance during antibiotic therapy: a multi-omic approach