Hobson C A, Vigue L, Naimi S, Chassaing B, Magnan M, Bonacorsi S, Gachet B, El Meouche I, Birgy A, Tenaillon O
IAME, UMR 1137, INSERM, Université de Paris, AP-HP, Paris, France.
INSERM U1016, Team 'Mucosal Microbiota in Chronic Inflammatory diseases', CNRS UMR 8104, Université de Paris, Paris, France.
JAC Antimicrob Resist. 2022 Jul 5;4(4):dlac077. doi: 10.1093/jacamr/dlac077. eCollection 2022 Aug.
Antimicrobial drugs are mostly studied for their impact on emergence of bacterial antibiotic resistance, but their impact on the gut microbiota is also of tremendous interest. gut models are important tools to study such complex drug-microbiota interactions in humans.
The MiniBioReactor Array (MBRA) microbiota system; a single-stage continuous flow culture model, hosted in an anaerobic chamber; was used to evaluate the impact of three concentrations of a third-generation cephalosporin (ceftriaxone) on faecal microbiota from two healthy donors (treatment versus control: three replicates per condition). We conducted 16S microbiome profiling and analysed microbial richness, diversity and taxonomic changes. β-Lactamase activities were evaluated and correlated with the effects observed in the MBRA system.
The MBRA preserved each donor's specificities, and differences between the donors were maintained through time. Before treatment, all faecal cultures belonging to the same donor were comparable in composition, richness, and diversity. Treatment with ceftriaxone was associated with a decrease in α-diversity, and an increase in β-diversity index, in a concentration-dependent manner. The maximum effect on diversity was observed after 72 h of treatment. Importantly, one donor had a stronger microbiota β-lactamase activity that was associated with a reduced impact of ceftriaxone on microbiota composition.
MBRA can reliably mimic the intestinal microbiota and its modifications under antibiotic selective pressure. The impact of the treatment was donor- and concentration-dependent. We hypothesize these results could be explained, at least in part, by the differences in β-lactamase activity of the microbiota itself. Our results support the relevance and promise of the MBRA system to study drug-microbiota interactions.
抗菌药物大多因其对细菌抗生素耐药性产生的影响而受到研究，但其对肠道微生物群的影响也备受关注。肠道模型是研究人类中此类复杂药物 - 微生物群相互作用的重要工具。
使用MiniBioReactor Array（MBRA）微生物群系统；一种置于厌氧箱中的单级连续流动培养模型，来评估三种浓度的第三代头孢菌素（头孢曲松）对两名健康供体粪便微生物群的影响（处理组与对照组：每个条件三个重复）。我们进行了16S微生物组分析，并分析了微生物丰富度、多样性和分类学变化。评估了β - 内酰胺酶活性，并将其与在MBRA系统中观察到的效应相关联。
MBRA保留了每个供体的特异性，并且供体之间的差异随时间保持。在处理前，属于同一供体的所有粪便培养物在组成、丰富度和多样性方面具有可比性。头孢曲松处理与α - 多样性降低和β - 多样性指数增加呈浓度依赖性相关。处理72小时后观察到对多样性的最大影响。重要的是，一名供体具有更强的微生物群β - 内酰胺酶活性，这与头孢曲松对微生物群组成的影响降低有关。
MBRA能够可靠地模拟肠道微生物群及其在抗生素选择压力下的变化。处理的影响具有供体和浓度依赖性。我们假设这些结果至少部分可以通过微生物群自身β - 内酰胺酶活性的差异来解释。我们的结果支持了MBRA系统在研究药物 - 微生物群相互作用方面的相关性和前景。
