Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease

Kohei Fukuoka; Yuya Yoshida; Kurumi Sotono; Naoki Nishikawa; Kengo Hamamura; Kosuke Oyama; Akito Tsuruta; Kota Mayanagi; Satoru Koyanagi; Naoya Matsunaga; Shigehiro Ohdo

doi:10.1016/j.bbrc.2023.07.015

Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease

Biochem Biophys Res Commun. 2023 Oct 1:675:92-98. doi: 10.1016/j.bbrc.2023.07.015. Epub 2023 Jul 10.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
² Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
³ Department of Glocal Healthcare Science, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
⁴ Department of Drug Discovery Structural Biology, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
⁵ Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address: matunaga@phar.kyushu-u.ac.jp.
⁶ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address: ohdo@phar.kyushu-u.ac.jp.

PMID: 37463524
DOI: 10.1016/j.bbrc.2023.07.015

Abstract

Chronic kidney disease (CKD) induces an imbalance in the intestinal microbiota, affecting various physiological functions and leading to cardiovascular inflammation and fibrosis. However, the cardiotoxic impact of intestinal microbiota-derived uremic substances in advanced renal dysfunction remains unexplored. Therefore, we developed a 5/6 nephrectomy (5/6Nx) mouse model to investigate the intestinal microbiota and the effects of administering vancomycin (VCM) on the microbiota and the cardiac pathology associated with CKD. Despite VCM administration after the development of irreversible glomerulosclerosis and tubulointerstitial fibrosis, blood indoxyl sulfate and phenyl sulfate levels, which are intestinal bacteria-derived uremic substances, brain natriuretic peptide levels, and the fibrotic area in the heart were decreased. Moreover, VCM administration prevented 5/6Nx-induced weight loss and prolonged survival time. Our findings suggest that VCM-induced changes in the intestinal microbiota composition ameliorate heart failure and improve survival rates by reducing intestinal microbiota-derived cardiotoxic substances despite advanced renal dysfunction. This highlights the potential of using the intestinal microbiota as a target to prevent and treat cardiovascular conditions associated with CKD.

Keywords: Chronic kidney disease; Heart failure; Intestinal microbiota; Uremic substance; Vancomycin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Fibrosis
Heart Failure* / drug therapy
Heart Failure* / etiology
Mice
Renal Insufficiency, Chronic* / complications
Renal Insufficiency, Chronic* / drug therapy
Vancomycin / therapeutic use

Substances

Vancomycin