Iodomethylcholine Inhibits Trimethylamine-N-Oxide Production and Averts Maternal Chronic Kidney Disease-Programmed Offspring Hypertension

You Lin Tain, Guo Ping Chang-Chien, Sufan Lin, Chih Yao Hou, Chien Ning Hsu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

Abstract

Chronic kidney disease (CKD) affects 10% of the global population, including pregnant women. Adverse maternal conditions determine the developmental programming of many diseases later in life. We previously demonstrated that adult rat offspring born to dams with CKD developed hypertension and renal hypertrophy. Trimethylamine-N-oxide (TMAO), a uremic toxin derived from the gut microbiota, has been linked to hypertension. This study assesses the effects of TMAO inhibition by iodomethylcholine (IMC) treatment on offspring hypertension programmed by maternal CKD. Female rats were fed either a control or a 0.5% adenine diet before conception, with or without IMC treatment during pregnancy and lactation. Maternal IMC treatment averted maternal CKD-primed offspring hypertension and renal hypertrophy in 12-week-old offspring. Offspring hypertension is associated with increases in the plasma TMAO concentration and oxidative stress and shifts in gut microbiota. The beneficial effects of IMC are related to a reduction in TMAO; increases in genera Acetatifactor, Bifidobacterium, and Eubacterium; and decreases in genera Phocacecola and Bacteroides. Our findings afford insights into the targeting of the gut microbiota to deplete TMAO production, with therapeutic potential for the prevention of offspring hypertension programmed by maternal CKD, although these results still need further clinical translation.

Original languageEnglish
Article number1284
JournalInternational Journal of Molecular Sciences
Volume24
Issue number2
DOIs
StatePublished - 09 01 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • chronic kidney disease
  • developmental origins of health and disease (DOHaD)
  • gut microbiota
  • hypertension
  • trimethylamine
  • trimethylamine-N-oxide
  • Humans
  • Rats
  • Renal Insufficiency, Chronic/drug therapy
  • Hypertension/prevention & control
  • Oxides/therapeutic use
  • Pregnancy
  • Animals
  • Female
  • Methylamines
  • Hypertrophy

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