Biointerface mineralization generates ultraresistant gut microbes as oral biotherapeutics

Abstract

Despite the fact that oral microecologics are effective in modulating the gut microbiome, they always suffer from multiple insults during the journey from manufacture to arrival at the intestine. Inspired by the protective mechanism of mineralization, we describe a cytocompatible approach of biointerface mineralization that can generate an ultraresistant and self-removable coating on bacterial surface to solve these challenges. Mineral coating endows bacteria with robust resistances against manufacture-associated oxygen exposure, ultraviolet irradiation, and 75% ethanol. Following oral ingestion, the coating is able to actively neutralize gastric acid and release encapsulated bacteria through spontaneous yet rapid double-decomposition reaction. In addition to acid neutralization, the generated calcium ions can trigger micellar aggregation of bile acid, enabling dual exemptions from the insults of gastric acid and bile acid to achieve uncompromised bacterial viability. Further supported by the therapeutic efficacy of coated bacteria toward colitis mice, biointerface mineralization provides a versatile platform for developing next-generation living oral biotherapeutics.

Calcium Tungstate Microgel Enhances the Delivery and Colonization of Probiotics during Colitis via Intestinal Ecological Niche Occupancy

“…We developed a probiotic delivery system that enhances the delivery and colonization of probiotics in colitis by occupying ecological niches in the intestine (Scheme ). IBD is largely caused by an imbalance in the gut-associated microbial community, characterized by an increase in Enterobacteriaceae and a decrease in probiotics. ,, Increasing evidence suggests that probiotics delivery can restore gut microbiota homeostasis to treat IBD. − However, in colitis, parthenogenic anaerobic Enterobacteriaceae proliferate and occupy ecological niches, restricting the colonization of probiotics. − Previous studies have attempted to administer antibiotics first, followed by probiotics, to create ecological niches for probiotic colonization . However, the use of antibiotics in IBD treatment also removes the beneficial intestinal microbes; this nonspecific strategy thus increases the risk expansion of harmful bacteria and antibiotic resistance.…”

Surface-modified bacteria: synthesis, functionalization and biomedical applications

“…6A). 134 In addition to protective coatings, intelligent coatings that can dissolve in response to the different local gastrointestinal environment changes and subsequently release the encapsulated bacteria at the target sites to exert efficacy have been developed. Eudragit polymers are pH-sensitive anionic copolymers comprising varying amounts of methacrylic acid and methyl methacrylate.…”

Advancement of Engineered Bacteria for Orally Delivered Therapeutics

“…eral coating can neutralize gastric acid and induce micellar aggregation of bile acid by released calcium ions, which greatly improved the viability of bacteria. [64] Furthermore, OMVs were engineered with biomimetic mineralization via growing calcium phosphate on the surface. The mineralized OMVs were sensitive to pH and help neutralize the acidic tumor microenvironment, resulting in highly beneficial polarization of macrophages for enhanced antitumor efficacy.…”