Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis

Probiotics are potential treatments for ulcerative colitis (UC), but their efficacy is frequently compromised by gastrointestinal conditions that limit adhesion and activity. Here, we use machine learning and bioinformatics to confirm that patients with UC have decreased prevalence of Lactobacillus genus and increased oxidative stress, which correlate with inflammation severity. Accordingly, we developed a probiotic-based therapeutic that synergistically restores intestinal redox and microbiota homeostasis. Lactobacillus casei (Lac) were induced to form a pericellular film, providing a polysaccharide network for spatially confined crystallization of ultrasmall but highly active selenium dots (Se-Lac). Upon oral administration, the selenium dot-embedded pericellular film efficiently enhanced gastric acid resistance and intestinal mucoadhesion of Lac cells. At the lesion site, the selenium dots scavenged reactive oxygen species, while Lac modulated the gut microbiota. In multiple mouse models and non-human primates, this therapeutic effectively relieved inflammation and reduced colonic damage, thus showing promise as a UC treatment.