Lactobacillus and Tryptophan Supplementation Improve Renal Function and are Associated with Metabolomic Alterations in a Mouse Model of Chronic Kidney Disease.

Abstract

Gut microbiota has been implicated in chronic kidney disease (CKD) progression. Probiotics such as Lactobacillus may alleviate renal injury through metabolic modulation, whereas tryptophan metabolism may have divergent effects in CKD. However, whether Lactobacillus and tryptophan supplementation are associated with distinct or overlapping metabolic profiles in CKD remains unclear. This study aimed to evaluate the effects of Lactobacillus and tryptophan supplementation and characterize the associated serum and fecal metabolomic alterations in an adenine-induced CKD mouse model. Six-week-old male mice were fed adenine for 3 weeks to induce CKD, followed by 8 weeks of treatment: saline for control (NC, CKD), Lactobacillus (2 × 107 CFU; CKD + Lac), or Tryptophan (4 mmol/kg; CKD + Try). Renal function markers (SCr, BUN, CysC), inflammatory markers (CRP, PCT), and histopathology were assessed at experimental endpoint (week 12). Serum and fecal metabolomics were analyzed using UPLC-HDMS, followed by PCA, OPLS-DA and KEGG pathway enrichment analyses. Adenine induced significant renal injury, as indicated by elevated SCr, BUN, CysC, CRP, and PCT levels, together with marked interstitial fibrosis and tubular epithelial degeneration. These alterations were partially attenuated by either Lactobacillus or tryptophan supplementation. In CKD + Lac mice, 250 serum and 332 fecal metabolites were altered across 5 pathways, including tyrosine, β-alanine, and riboflavin metabolism, prolactin signaling, and ABC transporters. In CKD + Try mice, 310 serum and 381 fecal metabolites were changed, involving tyrosine, biotin, linoleic acid, and amino acid metabolism, prolactin signaling, lipolysis, and arginine biosynthesis. Both Lactobacillus and tryptophan supplementation partially improved renal function and attenuated renal injury in adenine-induced CKD mice and were associated with altered serum and fecal metabolite profiles involving tyrosine, arginine, and related metabolic pathways. Not applicable.