Effect of Vancomycin on the Gut Microbiome and Plasma Concentrations of Gut-Derived Uremic Solutes
Lama Nazzal, Leland Soiefer, Michelle Chang, Farah Tamizuddin, Daria Schatoff, Lucas Cofer, Maria E. Aguero‐Rosenfeld, Albert Matalon, Björn Meijers, Robert S. Holzman, Jerome Lowenstein
Abstract
INTRODUCTION: Declining renal function results in the accumulation of solutes normally excreted by healthy kidneys. Data suggest that some of the protein-bound solutes mediate accelerated cardiovascular disease. Many of the poorly dialyzable protein-bound uremic retention solutes are products of gut bacterial metabolism. METHODS: We performed a blinded-randomized controlled trial comparing the changes in plasma concentrations of a panel of protein-bound solutes and microbiome structure in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 12 weeks in a cohort of stable patients with end-stage kidney disease. We also examined the pattern of recovery of the solutes and gut microbiome over 12 weeks of placebo administration following vancomycin. RESULTS: . We demonstrated microbiome recovery after stopping vancomycin. However, recovery in the solutes was highly variable between subjects. CONCLUSIONS: We demonstrated that microbiome suppression using vancomycin resulted in changes in multiple gut-derived uremic solutes. Future studies are needed to address whether reduction in those uremic solutes results in improvement of cardiovascular outcomes in ESKD patients.