BACKGROUND Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response. METHODS Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate ("co-amoxiclav"). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18). RESULTS Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera. CONCLUSIONS Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.

中文翻译：

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基线微生物群组成调节抗生素介导的对肠道微生物群和宿主的影响。

背景技术正常哺乳动物的发育和体内平衡取决于肠道微生物群。抗生素对于治疗和预防细菌感染至关重要，它可能会对肠道微生物群组成产生附带影响，进而对宿主产生深远且潜在的有害后果。然而，这种附带影响的程度和持续时间似乎因人而异。此外，目前尚不清楚这种扰动对宿主反应的影响程度。我们的目的是检验以下假设：不同的人类微生物组对常用抗生素有不同的反应，并且这些差异可能会影响宿主的反应。方法 用两个无关供体（A 和 B）的微生物群进行人源化的无菌小鼠（n = 30）接受阿莫西林克拉维酸（“co-amoxiclav”）为期 7 天的抗生素攻击。在抗生素使用前（第 0 天）和使用后（第 8 天）以及随后的恢复期（第 11 天和 18 天）进行微生物组和结肠转录组分析。结果 根据供体的不同，独特的群落特征很明显，供体 A 受体小鼠以普雷沃氏菌属和粪杆菌属为主，供体 B 受体小鼠以拟杆菌属和副拟杆菌属为主。抗生素治疗后，供体 A 小鼠的微生物群明显不稳定，而供体 B 小鼠则保持了更稳定的特征。在两组中接受抗生素攻击后，宿主转录组发生了明显的显着且重叠的变化。尽管存在这种重叠，供体 A 小鼠的基因表达发生了更显着的变化，并且独特地显示了宿主途径和关键微生物属之间的相关性。结论 由不同供体微生物群人源化的无菌小鼠保持了不同的微生物组特征，它们以不同的方式对抗生素挑战做出反应，并表现出与微生物组不平衡平行的宿主反应。这些结果表明，肠道微生物群的个体间差异可能有助于微生物群扰动后的个体化宿主反应。