<i>Bifidobacterium longum</i> subsp. <i>longum</i> CCFM1375 Mitigates Chronic Kidney Disease Progression via Gut Microbiota Modulation and Gut Barrier Restoration

ABSTRACT Chronic kidney disease (CKD) is associated with impaired kidney function, intestinal barrier dysfunction, accumulation of uremic toxins, and gut microbiota dysbiosis. In this study, we used an adenine‐induced CKD mouse model to evaluate the effects of Bifidobacterium longum subsp. longum CCFM1375 on CKD progression. Mice with CKD displayed increased serum creatinine and blood urea nitrogen (BUN) levels, kidney tissue histopathological injury, disrupted intestinal barrier integrity, elevated lipopolysaccharides (LPS) levels, and changes in gut microbiota composition. Intervention with B. longum subsp. longum CCFM1375 significantly alleviated these symptoms. Bifidobacterium longum subsp. longum CCFM1375 enhanced gut barrier function by upregulating tight junction proteins (ZO‐1, ZO‐2) and reducing pro‐inflammatory cytokines (IL‐6, TNF‐α), thereby lowering serum LPS levels. Metagenomic analysis revealed that B. longum subsp. longum CCFM1375 restored the gut microbial structure, increasing beneficial species such as Faecalibaculum rodentium, Asaccharobacter celatus, Adlercreutzia equolifaciens , while reducing potential pathogens. Furthermore, metabolic analysis showed that gut microbiota metabolic functions shifted from urea production to amino acid biosynthesis, significantly increasing fecal tryptophan and tyrosine levels and elevating serum glutamate content, potentially alleviating CKD progression by reducing urea production and ammonia toxicity. The intervention also enhanced thiamine synthesis and increased fecal cholic acid levels, significantly reducing serum uremic toxin levels, including trimethylamine N‐oxide, phenyl sulfate, and the indoleacetic acid precursor indole‐3‐pyruvic acid. In conclusion, B. longum subsp. longum CCFM1375 may delay CKD progression by repairing the intestinal barrier, modulating nitrogen metabolism pathways, and reducing uremic toxin accumulation, providing new evidence for the use of probiotics in kidney disease intervention.