Lee Imchang, Kim Bong-Soo, Suk Ki Tae, Lee Seung Soon
Division of Infectious Diseases, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea.
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea.
J Microbiol Biotechnol. 2025 Aug 7;35:e2406017. doi: 10.4014/jmb.2406.06017.
Carbapenem-resistant Enterobacteriaceae (CRE) represent a critical antimicrobial resistance threat due to their resistance to last-resort antibiotics and high transmission potential. While conventional strategies-such as infection control, antimicrobial stewardship, and novel antibiotic development-remain essential, growing attention has shifted toward the gut microbiome, which plays a central role in mediating colonization resistance against CRE. Disruption of the intestinal microbiota-primarily driven by antibiotic exposure and further exacerbated by non-antibiotic drugs such as proton pump inhibitors-reduces microbial diversity and impairs functional integrity, facilitating CRE acquisition, prolonged carriage, and horizontal transmission. In response, microbiome-based strategies-including microbiome disruption indices (MDIs), fecal microbiota transplantation (FMT), and rationally designed symbiotic microbial consortia-are being explored as novel approaches for CRE prevention and decolonization. Mechanistic studies have shown that colonization resistance is mediated by both direct mechanisms (, nutrient competition, short-chain fatty acid production) and indirect mechanisms (, immune modulation via IL-36 signaling). Advances in metagenomics, metabolomics, and culturomics have enabled high-resolution profiling of gut microbial communities and their functional roles. Emerging preclinical and clinical evidence supports the potential of microbiome-informed interventions to predict infection risk, enhance antimicrobial stewardship, and guide the development of next-generation probiotics targeting CRE. Longitudinal studies continue to evaluate the efficacy of FMT and synthetic microbial consortia in eradicating intestinal CRE colonization. Collectively, these insights underscore the promise of gut microbiome science as a complementary and innovative strategy for CRE control in the post-antibiotic era.
耐碳青霉烯类肠杆菌科细菌（CRE）因其对最后手段抗生素的耐药性和高传播潜力而构成严重的抗菌药物耐药性威胁。虽然传统策略，如感染控制、抗菌药物管理和新型抗生素研发，仍然至关重要，但越来越多的关注已转向肠道微生物群，它在介导对CRE的定植抗性方面发挥着核心作用。肠道微生物群的破坏主要由抗生素暴露驱动，并因质子泵抑制剂等非抗生素药物而进一步加剧，这会降低微生物多样性并损害功能完整性，从而促进CRE的获得、长期携带和水平传播。作为应对措施，基于微生物群的策略，包括微生物群破坏指数（MDIs）、粪便微生物群移植（FMT）和合理设计的共生微生物群落，正在作为预防和消除CRE的新方法进行探索。机制研究表明，定植抗性由直接机制（如营养竞争、短链脂肪酸产生）和间接机制（如通过IL-36信号传导进行免疫调节）介导。宏基因组学、代谢组学和培养组学的进展使得能够对肠道微生物群落及其功能作用进行高分辨率分析。新出现的临床前和临床证据支持基于微生物群的干预措施在预测感染风险、加强抗菌药物管理以及指导针对CRE的下一代益生菌开发方面的潜力。纵向研究继续评估FMT和合成微生物群落根除肠道CRE定植的疗效。总体而言，这些见解强调了肠道微生物群科学作为抗生素后时代控制CRE的补充性和创新性策略的前景。
