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Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens. However, biological challenges 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 in a novel mode. The hydrogel was prepared simply by the self-cross-linking of thiolated hyaluronic acid. Upon exposure to H 2 S which were excreted by surrounding intestinal pathogens, the hydrogel can locally degrade and rapidly release cargos to compete with source pathogens in turn for binding to the host. 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 optimal encapsulation system was further measured by a scanning electron microscope, exhibiting uniform payload of probiotics. Endurance experiments indicated that the encapsulation of L. rhamnosus significantly enhanced their viability under gastrointestinal tract insults. Compared with free cells, encapsulated L. rhamnosus exerted better therapeutic effect against Salmonella-induced enteritis with negligible toxicity in vivo. These results demonstrate that this redox-responsive hydrogel may be a promising encapsulation and delivery system for improving the efficacy of orally administered probiotics.

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