Protective Effects of Bifidobacterium bifidum Strains with IgA-Potentiating Activity Against ETEC Infection in Weanling Mice.

Enterotoxigenic Escherichia coli (ETEC) remains a leading cause of diarrheal morbidity and mortality in infants and young children worldwide. Weanling infants are particularly vulnerable due to the loss of maternal immunoglobulin A (IgA) protection and insufficient endogenous IgA production. Bifidobacterium bifidum FL228.1 and FL276.1 have been identified as strains capable of enhancing intestinal IgA levels in healthy weanling mice; however, their protective efficacy under pathogenic challenge was unknown. In this study, these strains were evaluated in an ETEC-infected weanling mouse model. Oral supplementation with FL228.1 or FL276.1 was associated with elevated small intestinal IgA levels (29.30% and 19.27%, respectively) and increased numbers of IgA⁺ cells (1.85-fold and 1.67-fold) compared with uninfected controls. Notably, both interventions markedly reduced ETEC load, alleviated growth retardation, mitigated intestinal tissue injury, and reduced systemic inflammatory responses. In addition, the probiotics counteracted ETEC-induced gut dysbiosis by restricting the overgrowth of pathogenic taxa (e.g., Escherichia-Shigella) and preserving beneficial populations (e.g., norank_f__Muribaculaceae). These results indicate that FL228.1 and FL276.1 confer protection against ETEC infection in weanling mice, an effect associated with their IgA-potentiating activity alongside modulation of inflammation, barrier function, and gut microbiota composition.