Abstract: TH-PO808
Investigating the Kidney-Gut-Brain Axis in CKD: Effects of High Amino Acids Diet With/Without Antibiotic Therapy
Session Information
- Health Maintenance, Nutrition, Metabolism
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance‚ Nutrition‚ and Metabolism
- 1400 Health Maintenance‚ Nutrition‚ and Metabolism
Authors
- Zhao, Yitong, University of California Irvine, Irvine, California, United States
- Liu, Han, University of California Irvine, Irvine, California, United States
- Tran, Tiffany, University of California Irvine, Irvine, California, United States
- Fisher, Mark, University of California Irvine, Irvine, California, United States
- Lau, Wei Ling, University of California Irvine, Irvine, California, United States
Background
Chronic kidney disease (CKD) has been associated with increased brain microhemorrhages in humans and in animal models. The altered gut microbiome in CKD contributes to the accumulation of uremic toxins such as p-cresyl sulfate (pCS), indoxyl sulfate (IS) and trimethylamine N-oxide (TMAO), which are derived from amino acid catabolism. We hypothesize that these vascular toxins increase brain microhemorrhages, and that suppression of the gut microbiome with broad-spectrum antibiotics in drinking water (Abx) will modify this outcome.
Methods
Male C57Bl/6J mice were randomized to control or CKD groups. CKD was induced with 0.2% adenine diet. Subgroups of mice were fed a high amino acids diet (HAA: 1.26% tryptophan, 2.88% phenylalanine & 0.6% choline) with/without Abx (ampicillin 1g/L, vancomycin 500 mg/L, neomycin sulfate 1g/L & metronidazole 1g/L). Levels of creatinine, cystatin C and uremic toxins were measured in serum samples. Microhemorrhage quantification was done via brain histology with Prussian blue staining, and stool was analyzed for microbial diversity. Data were analyzed using ANOVA.
Results
Levels of creatinine and cystatin C were significantly increased in CKD vs control animals and were decreased with Abx water consumption in CKD mice. Consumption of Abx changed the composition of microbiota in the stool samples. More Lactobacillus was observed in CKD and CKD+HAA mice compared to controls. There was an increased abundance of Akkermansia on the HAA diet, and Abx treatment markedly increased gut Enterobacter while suppressing other bacterial taxa. Levels of the uremic toxins pCS, IS and TMAO were significantly increased in CKD groups compared to controls, and TMAO was further increased on the HAA diet. Consumption of Abx in drinking water significantly reduced levels of all 3 toxins and the number of brain microhemorrhages (see table).
Conclusion
Broad-spectrum oral antibiotics treatment altered the gut microbiome, suppressed serum uremic toxins, and reduced brain microhemorrhage development in CKD mice.
Funding
- Other NIH Support