Abstract: SA-PO0326
Restoring Gut Microbial Balance via Fecal Transplantation Attenuates Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Almoussawi, Sarah, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Lawandos, Leonard, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Ghoussainy, Rawane, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Hamade, Sarah, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Alkhansa, Sahar, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Dia, Batoul, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Noureldein, Mohamad, American University of Beirut, Beirut, Beirut Governorate, Lebanon
- KFoury, Hala M., American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Ziyadeh, Fuad N., American University of Beirut, Beirut, Beirut Governorate, Lebanon
- Liagre, Bertrand, Universite de Limoges, Limoges, Aquitaine-Limousin-Poitou-Charentes, France
- Eid, Assaad Antoine, American University of Beirut, Beirut, Beirut Governorate, Lebanon
Background
Emerging evidence implicates gut dysbiosis as a key contributor to systemic inflammation and insulin resistance in type 2 diabetes (T2D). The gut-kidney axis has gained increasing attention as a modifiable driver of renal injury in Diabetes. Gut-derived metabolites such as lipopolysaccharides, uremic toxins, and short-chain fatty acids have been shown to influence oxidative stress, inflammation, and fibrotic responses in the kidney. We hypothesized that restoration of microbial homeostasis by fecal microbiota transplantation (FMT) from healthy donors could mitigate DKD progression and offer a novel therapeutic strategy.
Methods
Non-obese diabetic MKR mice and FVB/NJ controls were assigned to three groups: Sham, FMT from T2D donors, or FMT from healthy controls. Antibiotic pretreatment was used to deplete resident microbiota before initiating oral FMT twice weekly for 8 weeks. Renal function, histological analysis, and molecular profiling were assessed. Gut microbial composition was analyzed by 16S rRNA sequencing, and fecal and serum metabolites were evaluated using untargeted metabolomics.
Results
FMT from T2D donors into wild-type mice induced significant renal dysfunction, evidenced by elevated UACR, glomerular hypertrophy, mesangial expansion, and increased collagen deposition. These mice exhibited elevated renal ROS, NOX4 expression, and proinflammatory cytokines (TNF-α, IL-6, IL-1β). Similar findings were observed in untreated MKR mice. Conversely, MKR mice receiving healthy FMT showed reduced albuminuria, attenuated glomerular injury, and decreased fibrotic markers. This was accompanied by lower NOX4 levels, reduced oxidative stress, and suppression of inflammatory cytokines. Microbiome analysis revealed increased richness and altered abundance of key taxa in treated mice, along with favorable shifts in metabolites associated with anti-inflammatory and antioxidative pathways.
Conclusion
These findings provide evidence that gut dysbiosis contributes to DKD pathogenesis and that targeting the gut-kidney axis using FMT can restore renal homeostasis. Modulating the microbiome may represent a viable adjunct therapeutic approach in DKD.