Abstract: FR-PO0218
Effect of CKD-Specific Probiotic Strain KT-301 on Uremic Toxin-Induced Dysbiosis Using Human Intestinal Microbial Ecosystem Simulator (SHIME) Reactor Technology and Gut-Barrier Coculture System
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 2
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Vyas, Usha N., Kibow Biotech, Exton, Pennsylvania, United States
- Segal, Robert, Kibow Biotech, Exton, Pennsylvania, United States
Background
In CKD the accumulation of uremic toxins leads to microbial gut dysbiosis leading to disruption of gut barrier integrity, production of gut-generated toxins and systemic inflammation, reported to contribute to CKD progression. Using a model of the human gastrointestinal tract and a gut-barrier co-culture system, in vitro studies were performed to evaluate the beneficial effects of the probiotic KT-301 currently under clinical investigation in CKD Stage 4.
Methods
The standard SHIME reactor was adapted to a Triple-L configuration with only proximal (PC) and distal colon (DC). Microbiota of a healthy adult human donor was fed and dysbiosed with a cocktail of uremic toxins and increased pH. The probiotic KT-301 (3 specific probiotic strains and 2 prebiotic fibers) was fed to the SHIME units. At different time intervals samples from the PC and DC were analyzed for microbial metabolic activity, including short chain fatty acid (SCFA) production, uremic toxin reduction and altered gut microbiome profile. GC, LC-MS, shotgun sequencing was used. To assess the gut barrier integrity a cell culture model of CaCo2/THP1 was used. Samples from the SHIME treatment and control groups were fed to the cell culture. Pro and anti-inflammatory markers and TEER were measured. Statistical analysis used GraphPad Prism ver 10.0.
Results
At the end of the 3-week treatment period the SCFA propionate and butyrate increased by 21% and 19%, respectively compared to control. Significant reduction in urea in PC and DC (p<0.001) were seen, and PC p-cresyl sulfate (p<0.0001). Shifts in microbial communities were seen. Lachnospiraceae and Bifidobacteriaceae family increased as seen by jitter plots. Higher alpha diversity was seen in the PC. LEfSe showed increase in Lachnospiraceae and B. longum and decrease in Vellionella spp in PC. Increase in levels of C. minuta (DC) and reduction in A. insuavis were seen. The Caco-2/THP1 co-culture assays showed a decrease in the IL-1β (p<0.01 in PC) and increase in IL-6 (p<0.01 in PC and DC) and IL-10 (p<0.05 in PC, p<0.0001 in DC). No effect was seen on NF-kβ levels.
Conclusion
Multiple benefits were seen when adding KT-301 to the dysbiotic SHIME reactor and in the gut barrier coculture system, supporting observations from the KT-301 Phase 2b CKD Stage 4 study in slowing CKD progression.
Acknowledgment
Natarajan Ranganathan (in memoriam) and Pari Ranganathan (Kibow Biotech)
Funding
- Commercial Support – Kibow Biotech, LLC