Calcium‐Powered Probiotics Reconfigure the Intestinal Niche via Biofilm Transformation

ABSTRACT Excessive Desulfovibrio (Des) forms biofilm to enable dominant occupation of the intestinal niche, representing a common pathogenic driver of multiple inflammatory bowel disease (IBD) types. Colonization resistance constitutes the primary barrier to antagonistic probiotic efficacy, and this is driven by the pathogen‐favorable microenvironment established by Des. Here, probiotic Lactiplantibacillus (Lap) is modified by calcium ions (Ca 2+ ) and calcium‐regulative polyphenol (kaempferol‐3‐O‐rutinoside, KAE) via coordinate interaction to achieve intestinal niche reconfiguration. Targeting the tripartite mechanisms of Des‐mediated colonization resistance, the Ca 2+ /KAE@Lap platform optimized niche competition through Ca 2+ ‐bridged interfacial binding with directional bactericidal activity, and this enables bacterial replacement at occupied sites. Ca 2+ /KAE@Lap reestablishes calcium homeostasis disrupted by Des via synergistic Ca 2+ /KAE regulation, dually restoring epithelial energy metabolism and mucus layer reconstitution, counteracting Des‐induced colonized sites contraction and regenerated site impairment. This drives phenotypic shift in biofilm composition from Des‐dominated to Lap‐enriched consortia, which is concomitant with the redirection of intestinal colonization resistance from a pathogen‐permissive to a probiotic‐favored state. This calcium‐based biofilm transformation strategy overcomes the transient colonization limitation inherent in conventional probiotic therapies by effectively disrupting colonization resistance in IBD treatment.