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肠道真菌:抗生素治疗期间的间歇性变化和增殖。

Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment.

机构信息

University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania, United States of America.

出版信息

PLoS One. 2013 Aug 19;8(8):e71806. doi: 10.1371/journal.pone.0071806. eCollection 2013.

Abstract

Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract. The abundance of fungi and bacteria was measured using quantitative PCR, and the proportional composition of the communities quantified using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria dropped in abundance >3 orders of magnitude, so that the predominant 16S sequences detected became transients derived from food. Upon cessation of treatment, bacterial communities mostly returned to their previous numbers and types after 8 weeks, though communities remained detectably different from untreated controls. Fungal communities varied substantially over time, even in the untreated controls. Separate cages within the same treatment group showed radical differences, but mice within a cage generally behaved similarly. Fungi increased ∼40-fold in abundance upon antibiotic treatment but declined back to their original abundance after cessation of treatment. At the last time point, Candida remained more abundant than prior to treatment. These data show that 1) gut fungal populations change radically during normal mouse husbandry, 2) fungi grow out in the gut upon suppression of bacterial communities with antibiotics, and 3) perturbations due to antibiotics persist long term in both the fungal and bacterial microbiota.

摘要

人类使用抗生素与真菌的过度生长有关。在这里,我们使用了一种鼠模型,研究了万古霉素、氨苄西林、新霉素和甲硝唑治疗 76 天以及随后恢复期间的肠道微生物组。小鼠粪便被用作下消化道微生物群的替代物。使用定量 PCR 测量真菌和细菌的丰度,并使用 454/Roche 焦磷酸测序 rRNA 基因标签定量社区的比例组成。在治疗前,细菌的数量比真菌多 3 个数量级以上。在抗生素治疗后,细菌的丰度下降了 3 个数量级以上,以至于检测到的主要 16S 序列成为源自食物的瞬态。停止治疗后,细菌群落在 8 周后基本恢复到以前的数量和类型,但群落仍然与未处理的对照有明显的不同。真菌群落随时间变化很大,即使在未处理的对照组中也是如此。同一治疗组内的单独笼子显示出明显的差异,但同一笼子内的小鼠通常表现相似。抗生素治疗后真菌丰度增加了约 40 倍,但在停止治疗后又恢复到原来的丰度。在最后一个时间点,念珠菌仍然比治疗前更丰富。这些数据表明:1)肠道真菌种群在正常饲养小鼠时会发生剧烈变化;2)抗生素抑制细菌群落后,真菌在肠道中大量生长;3)抗生素引起的扰动在真菌和细菌微生物组中长期存在。

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