Nontoxigenic Bacteroides fragilis (NTBF) is defined by the absence of the bft gene and corresponding B. fragilis toxin production; however, nontoxigenic status alone does not establish uniform safety or probiotic function. This review critically evaluates strain-level biological characteristics, safety, mechanisms, metabolites, and disease-model evidence. Selected strains and defined strain-derived preparations, including ZY-312, HCK-B3, NCTC 9343-derived polysaccharide A, and ZY-312-derived zwitterionic capsular polysaccharide preparation TP2, have shown immunomodulatory, barrier-associated, and microbial-community-modulating activities, predominantly in vitro and in animal models. Direct causal evidence is limited to specific strain–preparation–host–model combinations, whereas many changes in cytokines, tight-junction-associated proteins, microbial composition, and organic-acid profiles remain functional or associative. Protective effects have been reported in preclinical models of inflammatory bowel disease, necrotizing enterocolitis, antibiotic-associated diarrhea, Clostridioides difficile infection, and enterotoxigenic B. fragilis (ETBF)-associated tumorigenesis. However, findings are highly dependent on the strain, preparation, dose, administration timing, host, and model. Safety remains incompletely resolved because the absence of B. fragilis toxin (BFT) does not exclude opportunistic or systemic infection, antimicrobial-resistance mobility, bacterial translocation, permeability changes, or adverse effects during long-term administration. Metabolic effects may also be beneficial or adverse depending on the strain, host dietary and genetic background, and experimental context. Human evidence is primarily observational, and robust intervention trials are lacking. Accordingly, NTBF should be regarded as a heterogeneous group of strain-specific live-biotherapeutic candidates requiring rigorous strain-specific manufacturing, potency, dose, antimicrobial-susceptibility, and safety evaluation.

Bovine coronavirus (BCoV) is a key pathogen causing calf diarrhea and bovine respiratory diseases, bringing sustained economic losses to the cattle industry. As an RNA virus, BCoV possesses high mutation and recombination capacities, leading to prominent genomic genetic diversity. The genome contains hypervariable and conserved regions, with the S (especially S1), HE and Open Reading Frame (ORF4) genes serving as major variation hotspots linked to viral antigenicity, tissue tropism shift and immune evasion. Host immune pressure drives strong positive selection on S protein antigenic variation. This review discusses existing research limitations and proposes future directions including genomic surveillance, reverse genetics verification and broad-spectrum vaccine development to support BCoV prevention and control.