Mus musculus strain:C57BL/6 Raw sequence reads

Although antibiotics are central to the treatment of bacterial infections, their use causes significant disturbances in the gut microbiota and development of antibiotic resistance. Thus, innovative administration methods for delivering antibiotics that avoid side effects on microbiota are urgently needed. Here, we report a positive lipid-assisted polymeric vesicular nanocarrier with a glucosylated surface (Positive Glucosylated Nanoparticles, PGNPs) that facilitates targeted absorption of antibiotics in the proximal small intestine by exploiting the highly specific expression of the sodium-dependent glucose transporter 1 (SGLT1) protein. We show that PGNPs-loaded antibiotics (PGNPs-Abx) effectively eliminated Streptococcus pneumoniae infection in lung. Importantly, compared to standard administration of the same antibiotics, oral administration of PGNPs-Abx markedly decreased adverse effects on the intestinal microbiota; lowered both dysbiosis-associated metabolic syndrome and infection; and reduced the accumulation of known antibiotic resistance genes in commensal bacteria. Our study thus demonstrates a convenient administration method for targeted absorption of antibiotics that confers efficacy against cold-associated Streptococcus pneumoniae infection, while driving less dysbiosis and its associated risk of systemic diseases.

抗生素是细菌感染治疗的核心手段，但该类药物的使用会显著扰动肠道微生物群，并催生抗生素耐药性。因此，亟需开发能够避免对微生物群产生不良影响的新型抗生素给药策略。本研究报道了一种表面糖基化的阳性脂质辅助聚合物囊泡纳米载体（Positive Glucosylated Nanoparticles，PGNPs），其可借助钠依赖性葡萄糖转运蛋白1（sodium-dependent glucose transporter 1，SGLT1）的高特异性表达特性，实现抗生素在近端小肠的靶向吸收。研究证实，负载抗生素的PGNPs（PGNPs-Abx）可有效清除肺部的肺炎链球菌（Streptococcus pneumoniae）感染。值得关注的是，与相同抗生素的标准给药方案相比，口服PGNPs-Abx可显著降低对肠道微生物群的不良影响；同时缓解与菌群失调相关的代谢综合征与感染，并减少共生细菌中已知抗生素耐药基因的积累。综上，本研究开发了一种便捷的抗生素靶向吸收给药方式，该方式可在维持抗感冒相关肺炎链球菌感染疗效的同时，大幅减轻菌群失调及其引发的全身性疾病风险。