d'Humières Camille, Delavy Margot, Alla Laurie, Ichou Farid, Gauliard Emilie, Ghozlane Amine, Levenez Florence, Galleron Nathalie, Quinquis Benoit, Pons Nicolas, Mullaert Jimmy, Bridier-Nahmias Antoine, Condamine Bénédicte, Touchon Marie, Rainteau Dominique, Lamazière Antonin, Lesnik Philippe, Ponnaiah Maharajah, Lhomme Marie, Sertour Natacha, Devente Savannah, Docquier Jean-Denis, Bougnoux Marie-Elisabeth, Tenaillon Olivier, Magnan Mélanie, Ruppé Etienne, Grall Nathalie, Duval Xavier, Ehrlich Dusko, Mentré France, Denamur Erick, Rocha Eduardo P C, Le Chatelier Emmanuelle, Burdet Charles
Université Paris Cité, IAME, INSERM, Paris, F-75018, France.
Institut Pasteur, Université Paris Cité, CNRS UMR3525, Microbial Evolutionary Genomics, Paris, 75015, France.
Microbiome. 2024 Mar 12;12(1):50. doi: 10.1186/s40168-023-01746-0.
Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience.
While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools.
In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. Video Abstract.
众所周知，抗生素会扰乱肠道微生物群。我们对健康志愿者使用头孢噻肟或头孢曲松治疗3天，并在每位受试者身上收集直至第90天的12份粪便样本。我们采用非靶向和靶向的表型及基因型方法，研究了微生物群的细菌、噬菌体和真菌成分的变化，以及粪便的代谢组和β-内酰胺酶活性。这使得我们能够评估它们的扰动程度和恢复力。
虽然只有两名受试者的粪便中可检测到抗生素浓度，这表明肠道中存在重要的抗生素降解现象，但静脉治疗对细菌和噬菌体微生物群以及代谢组的组成产生了非常显著的扰动。相比之下，治疗对真菌微生物群的影响相对较小。在监测期结束时，我们发现整个肠道系统存在恢复力的证据，因为即使细菌微生物群的结构发生了变化，且不同成分随时间的动态变化很少相关，但大多数成分仍恢复到了初始状态。观察到的抗生素抗性基因库的丰富度在第30天之前显著降低，而在第10天之前观察到编码β-内酰胺酶的基因相对丰度显著增加，这与微生物群β-内酰胺酶活性的相应增加一致。基线时的β-内酰胺酶活性水平与粪便代谢组含量的恢复力呈正相关。
在健康成年人中，抗生素会扰乱微生物群的许多成分，这些成分在30天内会恢复到接近基线的状态。这些数据表明，内源性产生β-内酰胺酶的厌氧菌在通过使到达结肠的抗生素失活来保护微生物群功能方面发挥着重要作用。视频摘要。
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