Abstract: FR-PO970
Effects of Lactobacillus rhamnosus GG on Gut-Derived Uremic Toxins and Gut Microbiome in Non-Dialysis CKD Patients
Session Information
- CKD Interventions: Trials and Quality Improvement
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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