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Kidney Week

Abstract: FR-PO970

Effects of Lactobacillus rhamnosus GG on Gut-Derived Uremic Toxins and Gut Microbiome in Non-Dialysis CKD Patients

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Tungsanga, Somkanya, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Treewatchareekorn, Sedthasith, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Kulvichit, Win, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Katavetin, Pisut, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Leelahavanichkul, Asada, Chulalongkorn University, Bangkok, Bangkok, Thailand
Background

Accumulation of uremic toxins in chronic kidney disease (CKD) is linked to progression to kidney failure via multiple mechanisms, including gut dysbiosis and gut-derived uremic toxins (GDUT) production. We explored the effects of Lactobacillus rhamnosus GG (GG), a probiotic, on GDUT and gut microbiome in CKD patients.

Methods

We conducted a randomized, double-blinded, controlled trial. After 2-week run-in, non-dialysis CKD stage 3-5 patients were assigned to receive LGG or placebo for 8 weeks and additional 12-week follow-up. Primary outcomes were changes in serum GDUTs (Indoxyl sulfate;IS, P-cresol sulfate;PCS) at end of treatment. Secondary outcomes included fecal microbiome analysis, serum inflammatory markers, eGFR, proteinuria, and adverse effects. In parallel, in vitro effects of E.coli lysate (ECL) with/without LGG-conditioned media (LCM) were explored in Caco-2 enterocytes and THP-1 macrophages.

Results

Among 60 participants (aged 70.15±12 years; 57% male; eGFR 38.17 ml/min/1.73m2), 30 each group, baseline characteristics were comparable. At the end of treatment, median changes in serum IS and PCS from baseline were lower in probiotic group (-0.89 vs +0.15 µmol/L, P<0.01) and (+0.1vs +1.0 µmol/L, P=0.01), respectively. Serum inflammatory markers were lower in probiotic group (endotoxin 0.29 vs 1.19 U/mL; P=0.02, IL-6 1.25 vs 2.52 pg/mL; P<0.01, and TNF-a 0.04 vs 0.36 pg/mL; P=0.02). The eGFR, proteinuria, and adverse effects were comparable. Fecal microbiome analysis in probiotic group showed decreased diversity and reduction in pathogenic Proteobacteria (Fig 1). In vitro, there were higher pro-inflammatory gene expression in Caco-2 and THP-1 cells with ECL, and lower enterocyte integrity. These effects were attenuated with LCM, indicating protective effects on enterocyte inflammation and integrity.

Conclusion

LGG improved gut dysbiosis, attenuated GDUT production, and reduced inflammatory responses linked to CKD progression. Probiotics may have a role in retarding CKD progression. Larger RCT is warranted.

Fecal microbiome analysis at end of treatment