如何保护肠道微生物群免受抗生素的影响? 基于PK-PD的创新策略,目标特异性和分子对药物的特性
Abhishek Rai1, Vaishnavi Newaskar1, Nibedita Roy1
1Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) S. A. S. Nagar (Mohali) Punjab 160062 India skguchhait@niper.ac.in.
RSC medicinal chemistry
|September 26, 2025
概括
新的抗生素策略专注于保护肠道微生物群,减少IBD和肥胖等副作用. 这些创新方法旨在尽量减少失生症,同时保持治疗疗效.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 药物发现 药物发现 药物发现
背景情况:
- 广谱抗生素破坏肠道微生物群,导致各种健康问题,包括IBD,感染和代谢障碍.
- 抗生素诱导的微生物群不平衡的长期后果,迫使开发出能够最大限度地减少肠道失调的策略.
研究的目的:
- 批判性地分析新兴的微生物群节约,基于药理动力学-药理动力学 (PK-PD) 的抗菌治疗策略.
- 突出针对特定目标的抗菌方法和新型临床候选人,尽量减少肠道微生物群的破坏.
主要方法:
- 基于PK-PD的创新策略的分析,包括选择性吸收,积累和吸收机制.
- 对针对特定细菌的抗菌方法进行审查,重点关注不同的细菌途径.
- 讨论具有病原体特异性疗效和有限肠道暴露的临床候选药物.
主要成果:
- 确定了几种微生物节约策略:载体介导吸收,排泄缺乏,pH依赖吸收,辅助疗法,β-乳酸酶选择性,免疫疗法和基于CRISPR的菌体疗法.
- 突出了针对细菌脂蛋白运输,脂肪酸生物合成,蛋白质生物合成 (MetRS) 和DNA复制 (DNA聚合酶IIIC) 的特定目标方法.
- 讨论了临床候选药物,如afabicin,lolamicin和其他具有病原体特异性作用和最小肠道影响的药物.
结论:
- 下一代抗菌药物设计必须优先考虑保护肠道微生物群的策略.
- 针对特定细菌途径和利用新型分子特征的创新方法对于预防抗生素相关失生症至关重要.
- 开发有效的抗菌剂以减少肠道暴露是保持肠道健康和最大限度地提高治疗结果的关键.
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