Abstract: FR-PO305
Role of Gut Microbiota in the Development of Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | 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, Lebanon
- Lawandos, Leonard, American University of Beirut, Beirut, Lebanon
- Hamade, Sarah, American University of Beirut, Beirut, Lebanon
- Shouman, Taghreed, American University of Beirut, Beirut, Lebanon
- Alkhansa, Sahar, American University of Beirut, Beirut, Lebanon
- Dia, Batoul, American University of Beirut, Beirut, Lebanon
- Noureldein, Mohamad, American University of Beirut, Beirut, Lebanon
- Eid, Assaad Antoine, American University of Beirut, Beirut, Lebanon
Background
The role of microbiota in Diabetes Mellitus (DM) and its complications has garnered significant attention recently. Our research highlighted that DM is associated with intestinal dysbiosis, characterized by decreased Bacteroidetes to Firmicutes ratio, the two main bacterial species constituting more than 90% of intestinal microorganisms. Interestingly, fecal microbial transplantation (FMT), i.e. the administration of fecal matter from a healthy donor into a recipient’s gastrointestinal tract, is emerging as a promising treatment approach for several diseases. Remarkably, reports established the capability of FMT to restore a healthy gut microbiome and alleviate symptoms of these diseases. Herein, we hypothesize that modifying gut microbiota by FMT might affect the pathogenesis and progression of diabetic kidney diseases (DKD) and serve as an effective treatment approach
Methods
FVB/NJ and non-obese type 2 diabetic MKR transgenic mice were used. Mice were divided into three groups: sham, group treated with FMT from healthy mice donors, and group treated with FMT from MKR diabetic donors. Treatment was administered by oral gavage twice weekly for 8 weeks after depleting their gut microbiota using an antibiotic cocktail. Urine and kidneys were collected for functional, histological, and molecular analyses
Results
Our study show a decline in kidney function, as evidenced by increased albuminuria (UAE) and urine albumin-creatinine ratio (UACR) in the FVB group treated with MKR FMT. Histological changes were also observed, along with elevated reactive oxygen species (ROS) production and inflammation, underscoring the presence of dysbiosis in renal deterioration. These findings closely mirrored the results observed in the MKR group, where elevated albuminuria levels and UACR were accompanied by increased sclerosis and collagen deposition, and paralleled by increased NOX induced ROS production and inflammation.
Intriguingly, these adverse effects were reversed in the MKR group treated with FVB FMT. This reversal was associated with reduced ROS production, decreased expression of NADPH oxidase (NOX), and dampened inflammation. Notably, the expression of inflammatory cytokines was significantly lower in this group
Conclusion
This study presents novel findings on the impact of microbiota in diabetes-induced renal injury