抗生素引起的肠道微生物群紊乱改变了人类对疫苗的免疫力，这一成果由美国斯坦福大学Bali Pulendran小组取得。相关论文2019年9月5日发表在《细胞》上。

研究人员在季节性流感疫苗接种前后向健康成人施用了广谱抗生素。尽管肠道细菌负荷减少了10000倍并且细菌多样性持续减少，但抗体反应没有受到显著影响。然而，在第二次试验中具有低预先存在的抗体滴度的受试者里，H1N1特异性中和和结合IgG1和IgA应答存在显著受损。此外，在这些研究中，抗生素治疗导致：（1）在老年人中观察到炎症特征的增加（包括AP-1/NR4A表达）以及树突状细胞活化的增加；（2）不同代谢轨迹，血清二级胆汁酸减少1000倍，这与AP-1/NR4A信号和炎性小体激活高度相关。多组学整合揭示了细菌物种与代谢表型之间的显著关联，突出了微生物组在调节人体免疫中的关键作用。

据悉，新兴的证据表明，微生物组在免疫方面具有核心作用。然而在人类中的因果证据却很少。

附：英文原文

Title: Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans

Author: Thomas Hagan, Mario Cortese, Nadine Rouphael, Carolyn Boudreau, Caitlin Linde, Mohan S. Maddur, Jishnu Das, Hong Wang, Jenna Guthmiller, Nai-Ying Zheng, Min Huang, Amit A. Uphadhyay, Luiz Gardinassi, Caroline Petitdemange, Michele Paine McCullough, Sara Jo Johnson, Kiran Gill, Barbara Cervasi, Jun Zou, Alexis Bretin, Megan Hahn, Andrew T. Gewirtz, Steve E. Bosinger, Patrick C. Wilson, Shuzhao Li, Galit Alter, Surender Khurana, Hana Golding, Bali Pulendran

Issue&Volume: Volume 178 Issue 6

Abstract: Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses. In addition, in both studies antibiotics treatment resulted in (1) enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (2) divergent metabolic trajectories, with a 1,000-fold reduction in serum secondary bile acids, which was highly correlated with AP-1/NR4A signaling and inflammasome activation. Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.

DOI: 10.1016/j.cell.2019.08.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30898-0