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Microcapsules for the synergistic delivery of probiotics and postbiotics from microfluidics for the treatment of colitis (I)
Bacterial metabolites have shown protective effects against colitis by regulating the gut microbiota, while the efficacy is limited by poor oral delivery efficiency and strict limitations on the use of single drugs. A novel synergistic delivery microcapsule of prebiotics and postbiotics has now been proposed, consisting of indole-3-propionic acid (IPA) postbiotics and three prebiotics: sodium alginate, resistant starch (RS), and chitosan. This microcapsule is used to prevent and treat colitis through microfluidic electrospray. The study found that oral administration of IPA microcapsules (IPA@MC) in mice has a significant protective effect against colitis, indicating the existence of a therapeutic synergistic effect between prebiotics and postbiotics. Furthermore, the mechanism of IPA@MC in regulating the gut microbiota significantly increases the overall abundance of bacteria that produce short-chain fatty acids (SCFAs), such as Faecalibacterium and Roseburia. These results suggest that the synergistic delivery microcapsules of prebiotics and postbiotics are ideal substances for treating colitis.
In this study, a novel prebiotic andpostbioticsynergistic delivery microcapsule is provided for the treatment of colitis. Prebiotics are indigestible dietary carbohydrates, including alginates, chitosan, inulin, etc., which have been widely used in diseases related to gut microbiota dysbiosis and as drug carriers. Postbiotics are small molecular metabolites other than prebiotics that play important roles in gut immune regulation, epithelial nutrition, and microbiota homeostasis. Among different postbiotics, tryptophan metabolites, including indole-3-propionic acid (IPA) and short-chain fatty acids (SCFAs), are the most attractive candidates for preventing and treating gastrointestinal diseases, including colitis, metabolic diseases, and cancer. A recent study also revealed that these metabolites regulate the gut barrier by modulating the gut microbiota, reducing inflammation by inhibiting HDAC and activating HAT in colon cells. However, studies have found that single postbiotics are insufficient to rebuild a healthy gut, leading to a low response to oral postbiotics for these diseases. Additionally, the oral delivery of water-soluble postbiotics suffers from low delivery efficiency in the gastrointestinal tract and limited overall therapeutic effects. This evidence suggests that the combined administration of prebiotics and postbiotics can help avoid colitis by increasing the abundance of beneficial bacteria produced by prebiotic fermentation in the gut and the levels of other postbiotics. Therefore, a more efficient and controllable delivery carrier for the combined administration of prebiotics and postbiotics is needed for the treatment of colitis. Microfluidics has been widely used to develop smart drug delivery systems. With advancements in microfluidic synthesis technology, lower molecular weight drugs can be encapsulated in prebiotic microcapsules, achieving controllable particle size distribution and formulation stability. These systems, such as microcapsules produced by microfluidics, can slow down the release of drugs in the acidic upper gastrointestinal tract after oral administration, thereby increasing the drug concentration in the lower gastrointestinal tract. Therefore, smart microfluidic microcapsules are believed to provide an effective venue for the combined delivery of prebiotics and postbiotics and offer a new platform for studying the synergistic effects of prebiotics and postbiotics in the treatment of colitis.

a) Microfluidic electrospray program for generating IPA-encapsulated Alg/RS microcapsules, which are further coated with chitosan. b) The dual pH-sensitive core-shell structure allows for slow drug release under acidic conditions in the upper gastrointestinal tract and rapid drug release under neutral conditions in the lower gastrointestinal tract, exerting protective effects against colitis by modulating the gut microbiota. Alg: alginate; RS: resistant starch; CS: chitosan; IPA: indole-3-propionic acid.
The required prebiotic microcapsules were generated using capillary microfluidic electrospray technology, and IPA postbiotics were encapsulated to prevent colitis. In vivo experiments showed that oral administration of IPA@MC provided significant protection against colitis compared to mice receiving prebiotics or postbiotics alone, indicating that the synergistic effect between prebiotics and postbiotics in IPA@MC offers a more effective treatment strategy for colitis. Additionally, the study indicated that IPA@MC can regulate the gut microbiome by significantly increasing the overall abundance and richness of bacteria that produce SCFAs, such as Faecalibacterium and Roseburia. Therefore, this synergistic delivery microcapsule of prebiotics and postbiotics is considered a promising candidate for the treatment of colitis.
Note: The article is translated from Prebiotics and Postbiotics Synergistic Delivery Microcapsules from Microfluidics for Treating Colitis.(For academic reference only)

Chuangyuan Biotechnology, probiotics, prebiotics, postbiotics, metabolites
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