Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
Center for Ecosystem Science and Society, Northern Arizona University, P.O. Box 5620, Flagstaff, AZ, 86011, USA; Department of Biological Sciences, Northern Arizona University, 617 S Beaver St., Flagstaff, AZ, 86011, USA.
EBioMedicine. 2024 Jan;99:104909. doi: 10.1016/j.ebiom.2023.104909. Epub 2023 Dec 13.
Escherichia coli sequence type 131 (ST131), specifically its fluoroquinolone-resistant H30R clade (ST131-H30R), is a global multidrug-resistant pathogen. The gut microbiome's role in ST131-H30R intestinal carriage is undefined.
Veterans and their household members underwent longitudinal fecal swab surveillance for ST131 in 2014-2018. The fecal microbiome was characterized by 16S rRNA qPCR and sequencing. We evaluated associations between ST131-H30R carriage and gut microbiome at baseline by random forest models to identify the most informative gut bacterial phyla and genera attributes for ST131 and ST131-H30R carriage status. Next, we assessed longitudinal associations between fecal microbiome and ST131-H30R carriage using a mixed-effects logistic regression with longitudinal measures.
Of the 519 participants, 78 were carriers of ST131, among whom 49 had ST131-H30R. At the baseline timepoint, H30R-positive participants had higher proportional abundances of Actinobacteria phylum (mean: 4.9% vs. 3.1%) than ST131-negative participants. H30R-positive participants also had higher abundances of Collinsella (mean: 2.3% vs. 1.1%) and lower abundances of Alistipes (mean: 2.1% vs. 2.6%) than ST131-negative participants. In the longitudinal analysis, Collinsella abundance correlated positively with ST131-H30R carriage status and negatively with the loss of ST131-H30R. Conversely, Alistipes corresponded with the loss and persistent absence of ST131-H30R even in the presence of a household exposure.
Abundances of specific fecal bacteria correlated with ST131-H30R carriage, persistence, and loss, suggesting their potential as targets for microbiome-based strategies to reduce carriage of ST131-H30R, a significant risk factor for invasive infections.
This work was supported in part by National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R21AI117654 and UM1AI104681 and the Office of Research and Development, Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.
大肠杆菌序列型 131（ST131），特别是其氟喹诺酮耐药 H30R 分支（ST131-H30R），是一种全球多药耐药病原体。肠道微生物组在 ST131-H30R 肠道携带中的作用尚未明确。
退伍军人及其家庭成员于 2014 年至 2018 年期间接受了 ST131 的纵向粪便拭子监测。通过 16S rRNA qPCR 和测序对粪便微生物组进行了特征描述。我们通过随机森林模型评估了 ST131-H30R 携带状态与基线时肠道微生物组之间的关联，以确定对 ST131 和 ST131-H30R 携带状态最有信息的肠道细菌门和属属性。接下来，我们使用带有纵向测量的混合效应逻辑回归评估了粪便微生物组与 ST131-H30R 携带之间的纵向关联。
在 519 名参与者中，有 78 名携带 ST131，其中 49 名携带 ST131-H30R。在基线时间点，H30R 阳性参与者的放线菌门比例较高（平均值：4.9%比 3.1%）。与 ST131 阴性参与者相比，H30R 阳性参与者的柯林斯菌属丰度更高（平均值：2.3%比 1.1%），而艾利希氏菌属丰度更低（平均值：2.1%比 2.6%）。在纵向分析中，柯林斯菌属丰度与 ST131-H30R 携带状态呈正相关，与 ST131-H30R 的丢失呈负相关。相反，即使存在家庭暴露，艾利希氏菌属也与 ST131-H30R 的丢失和持续缺失相关。
特定粪便细菌的丰度与 ST131-H30R 携带、持续存在和丢失相关，这表明它们可能成为基于微生物组的策略的目标，以减少 ST131-H30R 的携带，ST131-H30R 是侵袭性感染的一个重要危险因素。
这项工作得到了美国国立卫生研究院过敏和传染病研究所的部分支持，资助号为 R21AI117654 和 UM1AI104681，以及美国退伍军人事务部研究与发展办公室。内容仅由作者负责，不一定代表国立卫生研究院或美国退伍军人事务部的官方观点。
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