Lactobacillus rhamnosus L34 attenuates chronic kidney disease progression. - GreenMedInfo Summary

BACKGROUND: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation, and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 (L34) might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6-nephrectomy (5/6Nx) mice.

METHODS: At 6 weeks post-5/6Nx in mice, either L34 (1 × 106 CFU) or phosphate buffer solution (as 5/6Nx control) were daily fed for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical resistance; TEER) were assessed in Caco-2(enterocytes). In parallel, the effects as such on pro-inflammatory cytokines and collagen expression were assessed in HK2 proximal tubular cells.

RESULTS: At 20-weeks post-5/6Nx, L34-treated mice showed significantly lesser renal injuries, as evaluated by i) kidney fibrosis area (P < 0.01) with lower serum creatinine and proteinuria, ii) GDUT including trimethylamine-N-oxide (TMAO) (P = 0.02) and indoxyl sulfate (P < 0.01), and iii) endotoxin (P = 0.03) and serum TNF-α (P = 0.01), than 5/6Nx-controls. Fecal-microbiome analysis revealed an increased proportion of Bacteroidetes in 5/6Nx-controls. After incubation with indoxyl sulfate, Caco-2 enterocytes had higher IL-8, NFκB expression, and lower TEER value, and HK2 cells demonstrated higher gene expression of TNF-α, IL-6, and collagen (type III and type IV). These indoxyl sulfate-activated parameters were attenuated with L34-conditioned media indicating the protective role of L34 on enterocyte integrity and renal fibrogenesis.

CONCLUSION: Lactobacillus rhamnosus L34 attenuated uremia-induced systemic inflammation by reducing GDUTs and gut-leakage that provided reno-protective effects in CKD.