Abstract: FR-PO775
The Gut Microbiome Links to Metabolic Syndrome Following Kidney Transplantation
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Mannon, Peter J., University of Nebraska Medical Center, Omaha, Nebraska, United States
- Mannon, Roslyn B., University of Nebraska Medical Center, Omaha, Nebraska, United States
Background
The metabolic syndrome (MBS) contributes to cardiovascular morbidity and mortality following kidney transplantation. Gut microbiome dysbiosis impacts lipid metabolism, insulin resistance, atherosclerotic factors, and in kidney transplant recipients (KTRs), may be linked to alloimmunity. We hypothesized that changes in gut microbiome pre- and post-transplant are linked to the outcome of MBS in KTRs.
Methods
Stool specimens (pre and 6-12 months post) from 14 serial KRTs from living donors and 8 healthy controls had 16S rRNA gene sequencing, microbial metagenome analysis, and targeted (69 gut metabolites in serum and 104 fecal metabolites) and untargeted metabolomics. Clinical data were extracted from the EMR. The primary outcomes were differences in microbiome and metabolome pre-Tx vs control and vs post-Tx. Secondary outcomes were differences in microbiome and metabolome between pre-Tx vs post-Tx stratified by MBS status and if a microbiome or metabolome “signature” predicted MBS outcome in KTRs.
Results
11 KTRs met criteria for MBS pre-Tx, of which 8 were stable or worsened and 3 improved MBS post-Tx; 1 developed MBS de novo. Versus controls, pre-Tx gut microbiome were less diverse, with significantly ↑ E coli and Fusobacterium, ↑ CKD metabolites, and ↑ glutathione (oxidative stress) & proteolytic metabolic pathways with ↓Coprococcus and Roseburia and ↓ short chain fatty acids. Post-Tx microbiome showed significantly ↑ Roseburia with ↓ Akkermansia, ↓ uremic toxins, and ↓ proteolytic pathways. Untargeted metabolomics aligned with improvement in MBS post-Tx (Fig 1) and independently discriminated between MBS outcomes (Fig 2). Improved MBS post-Tx was associated with ↑ Ruminococcus, ↓Akkermsansia, and dominant saccharolytic, butyrogenic, and methanogenic pathways.
Conclusion
We found that the gut microbiome discriminates pre- and post-KTR MBS states and provides a signature of MBS post-Tx. These data support using targeted prebiotics and probiotics to confer a beneficial metabolic state pre-Tx and post-Tx to improve long term patient and graft survival.
Funding
- Private Foundation Support