Bifid triple viable tablets are associated with renal biochemical improvement and qualitative gastrointestinal changes in 5/6-nephrectomized rats: An exploratory microbiome-metabolome study.

BACKGROUND: Chronic kidney disease (CKD) is accompanied by renal injury, gut-barrier disruption, dysbiosis, inflammation, and disordered iron regulation. We examined whether a clinical multi-strain probiotic produces coordinated renal, intestinal, and metabolic effects in experimental CKD. METHODS: Male Sprague-Dawley rats underwent 5/6 nephrectomy (5/6 Nx). Dose-response phenotyping compared sham, untreated 5/6 Nx, three Bifid Triple Viable Tablets (BTV) doses, and valsartan (n = 3/group). Independent cohorts provided targeted validation (untreated versus high-dose BTV; n = 6/group) and paired fecal 16S rRNA/serum metabolomics (n = 4/group). Technical replicates were averaged within animals. RESULTS: High-dose BTV was associated with lower blood urea nitrogen (BUN), serum creatinine (Scr), inflammatory cytokines, and hepcidin, plus qualitatively less renal and gastrointestinal injury. Occludin and zonula occludens-1 (ZO-1) integrated fluorescence did not differ from untreated 5/6 Nx rats (all adjusted P > 0.05; n = 3/group). Validation confirmed lower BUN (27.87 ± 2.09 vs 16.64 ± 3.82 mmol/L; P = 0.000264), Scr (235.75 ± 27.41 vs 132.05 ± 19.50 μmol/L; P = 0.0000343), and interleukin-6 (IL-6; 188.11 ± 8.67 vs 92.21 ± 14.51 pg/mL; P = 5.72 × 10-7) with high-dose BTV. Omics detected 1966 metabolites, 393 differential metabolites, and 160 nominal genus-metabolite associations. CONCLUSIONS: BTV was associated with reproducible renal biochemical and inflammatory improvement, qualitative gastrointestinal differences, and exploratory microbial-metabolic changes. Barrier-protein findings were nonsignificant, and small, separate cohorts preclude causal inference.