發(fā)布者：抗性基因網(wǎng) 時間：2023-06-12 瀏覽量：291
摘要
? ? ? 抗生素對微生物組的附帶影響越來越受到關(guān)注。然而，長期接觸抗生素對腸道微生物組的生態(tài)影響，包括抗生素耐藥性，仍然有限。在這里，我們研究了長期接觸阿莫西林對人類腸道微生物組和耐藥性的影響。作為挪威慢性腰痛多中心臨床試驗（AIM研究）的一部分，從20名接受3個月阿莫西林或安慰劑治療的患者身上采集糞便樣本。在基線、治療的最后一天和抗生素停用后9個月采集樣本。利用全鳥槍和功能宏基因組測序數(shù)據(jù)對微生物和抗性組分的豐度和多樣性進(jìn)行了表征。雖然安慰劑受試者的微生物組特征隨著時間的推移是穩(wěn)定的，但在阿莫西林治療后觀察到多樣性和整體微生物組組成的明顯變化。特別是，與健康相關(guān)的短鏈脂肪酸產(chǎn)生物種的比例顯著下降。然而，這些變化是短暫的，因為微生物組在治療后9個月顯示出總體恢復(fù)。另一方面，長期暴露于阿莫西林與抗微生物耐藥性基因總載量和抗微生物耐藥基因多樣性的增加有關(guān)，即使在治療后9個月也會持續(xù)變化。此外，β-內(nèi)酰胺耐藥性是受影響最大的抗生素類別，這表明對阿莫西林有靶向反應(yīng)，盡管基因水平的變化因個體而異。總體而言，我們的研究結(jié)果表明，與微生物組組成相比，長期接觸阿莫西林對糞便耐藥組的影響更為明顯和持久。這些信息與設(shè)計合理的抗生素治療給藥指南有關(guān)。
ABSTRACT
The collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composition were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health-associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.
https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2157200