不同抗生素诱导的微生物群介导的肠道代谢物和免疫反应的显著变化。

Distinct Changes in Microbiota-Mediated Intestinal Metabolites and Immune Responses Induced by Different Antibiotics.

作者信息

Yoon Sunghyun, Lee Giljae, Yu Junsun, Lee Kiuk, Lee Kyeongju, Si Jiyeon, You Hyun Ju, Ko GwangPyo

机构信息

Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.

Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Republic of Korea.

出版信息

Antibiotics (Basel). 2022 Dec 6;11(12):1762. doi: 10.3390/antibiotics11121762.

Abstract

The cocktails of antibiotics are utilized to study the functions of microbiota. There have been studies on the alteration of not only the microbiota composition but also the host's metabolism or immunity. However, the bacterial species associated with these altered physiologic markers are still unclear. Therefore, we supplied mice with drinking water containing ampicillin (AMP), vancomycin (VAN), neomycin (NEO), or metronidazole (MET) to observe the effect of each antibiotic on helper T cells and inflammation-related gene expression and metabolism, including amino acid metabolism and changes in gut microbiota. We observed major changes in gut microbiota in mice treated with AMP and VAN, respectively, immediately after administration. The abundance of the genera and increased in the AMP and VAN groups, while almost disappeared from both groups. The compositional changes in intestinal metabolites in the AMP and VAN groups were more distinct than those in the NEO and MET groups, which was similar to the microbiome results. In particular, the most distinct changes were observed in amino acid related metabolism in AMP and VAN groups; the amounts of phenylalanine and tyrosine were increased in the AMP group while those were decreased in the VAN group. The changed amounts of intestinal amino acids in each of the AMP and VAN groups were correlated with increases in the abundance of the genera and in the AMP and VAN groups, respectively. The most distinctive changes in intestinal gene expression were observed in the ileum, especially the expression Th17-related genes such as , , and , which decreased dramatically in the guts of most of the antibiotic-treated groups. These changes were also associated with a significant decrease in in both the AMP and VAN groups. Taken together, these findings indicate that changes in gut microbiota as well as host physiology, including host metabolism and immunity, differ depending on the types of antibiotics, and the antibiotic-induced gut microbiota alteration has a correlation with host physiology such as host metabolic or immunological status. Thus, the immune and metabolic status of the host should be taken into account when administering antibiotics.

摘要

抗生素鸡尾酒被用于研究微生物群的功能。不仅有关于微生物群组成变化的研究,还有关于宿主代谢或免疫变化的研究。然而,与这些改变的生理标志物相关的细菌种类仍不清楚。因此,我们给小鼠提供含有氨苄青霉素(AMP)、万古霉素(VAN)、新霉素(NEO)或甲硝唑(MET)的饮用水,以观察每种抗生素对辅助性T细胞、炎症相关基因表达和代谢(包括氨基酸代谢)以及肠道微生物群变化的影响。给药后立即观察到,分别用AMP和VAN处理的小鼠肠道微生物群发生了主要变化。AMP组和VAN组中属 和 的丰度增加,而两组中 几乎消失。AMP组和VAN组肠道代谢物的组成变化比NEO组和MET组更明显,这与微生物组结果相似。特别是,在AMP组和VAN组中观察到氨基酸相关代谢的最明显变化;AMP组中苯丙氨酸和酪氨酸的量增加,而VAN组中则减少。AMP组和VAN组中肠道氨基酸的变化量分别与AMP组和VAN组中属 和 丰度的增加相关。在回肠中观察到肠道基因表达的最显著变化,特别是Th17相关基因如 、 和 的表达,在大多数抗生素处理组的肠道中显著下降。这些变化也与AMP组和VAN组中 的显著减少有关。综上所述,这些发现表明,肠道微生物群的变化以及宿主生理(包括宿主代谢和免疫)因抗生素类型而异,抗生素诱导的肠道微生物群改变与宿主生理(如宿主代谢或免疫状态)相关。因此,在使用抗生素时应考虑宿主的免疫和代谢状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/9774394/45f28e8623d1/antibiotics-11-01762-g001.jpg

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