Co-delivery of vitamin D and probiotics and their synergistic improvement of intestinal functions in simulated microgravity rats via zein/sodium caseinate-based microcapsules.

Long-term microgravity disrupts astronauts' intestinal homeostasis, causing gut dysbiosis, barrier injury and immune imbalance among other issues. Vitamin D (VD) and probiotics may provide synergistic protection, but their synchronous and stable gastrointestinal delivery remains a key challenge. In this study, zein and sodium caseinate (NaCas) were used as wall materials to fabricate Vitamin D3 (VD3)-loaded nanoparticles (ZND) by anti-solvent precipitation. ZND and Lactobacillus rhamnosus GG (LGG) were then co-encapsulated into microcapsules (ZND-loaded LGG microcapsules, ZND-L) via complex coacervation. ZND-L showed favorable physicochemical properties, good storage stability, high encapsulation efficiency, and high probiotic viability retention. It also exhibited gastrointestinal-environment-adaptive controlled release behavior. The microcapsules shell protected VD3 and LGG against acidic and bile-related stresses, reduced premature release under simulated gastric conditions, and enabled sustained release under simulated intestinal conditions. This design promoted distal intestinal delivery of bioactive VD3 and viable LGG. In the tail-suspension simulated microgravity rat model, ZND-L mitigated intestinal dysbiosis, restored intestinal barrier function by upregulating the expression of occludin (OCC), zonula occludens-1 (ZO-1) and secretory immunoglobulin A (sIgA), and further reshaped systemic immune homeostasis by reducing the production of pro-inflammatory cytokines. These benefits were associated with coordinated microbiota-barrier-immune regulation and improved VD3 metabolic signaling through activation of the vitamin D receptor (VDR) pathway. The combined microcapsules intervention outperformed single VD3 supplementation and administration of free LGG. It offers a promising strategy for maintaining intestinal health in microgravity environments and has the potential for application in the field of aerospace nutrition.