Abstract
Nutrient competition with indigenous microbes or pathogens presents a significant challenge for oral probiotic efficacy. To address this issue, we develop an ameba-inspired food-carrying strategy (AIFS) by prebinding ginger-derived exosome-like nanoparticles (GELNs) onto probiotics as food depots. AIFS enables probiotics to efficiently and exclusively consume GELNs in situ, even in the presence of competing bacteria. This results in up to 21 times higher uptake efficiency compared to unengineered probiotics, dramatically accelerating probiotic proliferation. Meanwhile, AIFS potentiates probiotics' resistance to multiple GI stressors. In a murine model of colitis, AIFS can improve the abundance of probiotics and inhibit pathogens, maintaining intestinal flora homeostasis. Additionally, it can upregulate the anti-inflammatory IL-10, reduce the proinflammatory IL-1β, and repair damaged intestinal mucus. Thereby, AIFS displays potently elevated prophylactic and therapeutic efficacy for colitis mice. This work provides a method for microbial engineering, with broad implications for microbiotherapy and gut health.