Design And Application Of Pathogen-targeted Probiotics Delivery System

Bacterial enteritis is one of the most common global health threats which usually accompanied by symptoms involving nausea,hematochezia and diarrhea.As the main clinical treatment for bacterial infections,current antimicrobial therapy suffers greatly from antibiotic-resistance crisis and toxic side effects in patients,emphasizing the urgent need for new approaches to mitigate bacterial enteritis.Attachment of pathogens on epithelial tissues has been recognized as the first step in infectious process,otherwise they will be expelled by the host’s physiological mechanical defense mechanisms.Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens.However,biological challenges（acidic conditions and bile salts）encountered during oral delivery have greatly limited their potential health benefits.Here,a model probiotic（Lactobacillus rhamnosus）was encapsulated in an intestinal-targeted hydrogel to alleviate bacterial enteritis.The hydrogel was prepared simply by self-crosslinking of thiolated hyaluronic acid.Upon exposure to H₂S which were excreted by surrounding intestinal pathogens,the hydrogel can locally degrade and rapidly release cargos to compete with source pathogens for binding to the host.The successful synthesis of HA-SH was verified by ¹HNMR and HPGPC respectively.The mechanical properties of hydrogel were studied by rheological analysis,and the ideal stability was achieved at a polymer concentration of 4%（w/v）.The morphology of the encapsulation system was further measured by SEM,exhibiting uniform payload of probiotics.Endurance experiments indicated that the encapsulation of Lactobacillus rhamnosus significantly enhanced their viability under gastrointestinal tract insults.Besides,the encapsulation technology can also improve shelf time of Lactobacillus rhamnosus when stored at refrigerated and ambient conditions.Compared with free cells,encapsulated Lactobacillus rhamnosus exerted better therapeutic effect against Salmonella-induced enteritis with negligible toxicity in vivo.In summary,this pathogen-targeted hydrogel could be a promising delivery system to effectively improve the oral efficacy of probiotics.Moreover,the probiotics therapy can alleviate the negative effects brought by antibiotics,which provides a new treatment for bacterial enteritis.