| Oral antibiotics are the most frequent and effective medical treatment for bacterial infection.However,during such treatment,the non-absorbed portion of orally administered antibiotics may reach the cecum and colon,where they can exert extreme perturbations of the human microbiota.The commensal residence in the human intestinal tract are known to impact many physiological processes and to participate in the regulation of immune and metabolic homeostasis.Thus,antibiotic exposure can alter basic physiological homeostasis or even contribute to chronic diseases such as allergies or obesity.In addition,excessive antibiotic use fosters the emergence of resistant strains,and human microbiota which have been repeatedly exposed to antibiotics represents a significant reservoir of antibiotics resistance genes;these are known to contribute to the increasing difficulty of controlling bacterial infections in the clinic.Therefore,it is of paramount importance to optimize the use of antibiotics,in minimizing its collateral adverse effects on the gut microbiota.Previous attempts to alter antibiotics regimens to protect the microbiota while preserving anti-pathogenic efficacy included the oral co-administration of a lactamases,thereby preventing some deleterious impacts of parenteral β-lactams on the microbiota.Other approaches include the addition of nonspecific absorbents such as activated charcoal,which upon delivery to the ileum or colon resulted in decreased fecal concentrations of orally administrated antibiotics,while not affecting their plasma pharmacokinetics.Systemic administration routes for antibiotics like intravenous injection do offer relative benefits in protecting the gut microbiota,but these are not suitable for use in the non-hospital settings.Therefore,it is of paramount importance to optimize the use of antibiotics,in minimizing its collateral adverse effects on the gut microbiota,alternative methods are urgently needed to manage the dysbiosis caused by orally administrated antibiotics.In our work,we proposed a new oral antibiotic administration method,which can effectively reduce the damage of antibiotics to intestinal symbiotic flora.Previous studies have shown that the abundance and composition of gut microbiota vary different regions of the intestine.The numbers of bacteria generally range from～105 per mL in the upper small intestine and up to 1012 per mL in the colon.According to this phenomenon,we report a strategy that enables spatial absorption of antibiotics in the proximal small intestine and thus avoid antibiotics contact with abundant intestinal flora in large intestine.Specifically,we discover that sodium-dependent glucose transporter 1(SGLT1)is highly expressed in the proximal small intestine.So,a positive glucosylated nanoparticle(PGNPs)approach is designed to be efficiently absorbed by proximal small intestine exploiting glucose-glucose transporter binding property,avoiding side effects on microbiota.The cationic and glucosylated surface enables PGNPs to target the intestinal mucus layer and epithelial cells in proximal small intestine,respectively.Therefore,using PGNPs to load antibiotics,not only increases the concentration of antibiotics in blood,but also effectively eliminates Streptococcus pneumoniae infection in lung and Listeria monocytogenes in blood.The present study demonstrates that treatment with PGNPs-antibiotics facilitates targeted absorption of antibiotics with reducing the destruction of intestinal flora,lowered both dysbiosisassociated opportunistic pathogen infection and metabolic syndrome,and reduced the accumulation of known antibiotic resistance genes in commensal bacteria.We will further improve the stability of the nanomaterial and the inclusion of different antibiotics.We hope that this work will eventually change the two main side effects of current antibiotic application on human body:the destruction of intestinal flora causing chronic diseases and the accumulation of drug resistance genes. |
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