Multi-functionalized probiotics through layer-by-layer coating with tannic acid-Mg2+ and casein phosphopeptide complexes for preventing ulcerative colitis

Gut microbiota imbalance-induced inflammatory response and oxidative stress are two of the main reasons causing ulcerative colitis (UC). Probiotics show potent modulating effects on microbiota imbalance and have been considered as an optimal substitute of antibiotics for preventing UC. However, the harsh environment of the gastrointestinal tract is not conducive to the survival and persistence of probiotics. Herein, we developed an efficient surface coating strategy to overcome the delivery challenges of probiotics and also endow them with multiple functions through layer-by-layer coating with tannic acid (TA)-Mg²⁺ and casein phosphopeptide (CPP) complexes. Saccharomyces boulardii (SB), one of yeasts that have been widely applied in the food and pharmaceutical field, was used as a model probiotic for assessing the synergistic effects of this coating strategy on preventing UC. Multi-functionalized probiotic thus prepared (called SB@TA-Mg²⁺@CPP) had significantly enhanced stability under the simulated gastric and intestinal fluid conditions, and also displayed vigorous cell viability and potent antioxidant activity. In the mouse model of dextran sulfate sodium (DSS)-induced colitis, SB@TA-Mg²⁺@CPP exhibited strong antioxidant and anti-inflammatory effects, remarkably increased the abundance and diversity of gut microbiota, and maintained gut barrier integrity. Meanwhile, SB@TA-Mg²⁺@CPP notably improved the adsorption of Mg²⁺, which also contributed to enhance the preventive effect against DSS-induced colitis. In summary, this study provides an efficient coating strategy to develop multi-functionalized probiotics for preventing UC.