Impact of Chronic Constipation and Subtypes on Serum Trimethylamine-N-Oxide Levels and Their Reduction With Treatment: Multicenter Observational Study.

INTRODUCTION

Chronic constipation (CC) is associated with increased cardiovascular events, and trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been recently shown to correlate with this risk. We examined how constipation status affects serum TMAO and how treatment modifies it.

METHODS

This was a prospective observational study (July 2023-September 2024) conducted at 3 Japanese centers. Healthy controls (HCs) were recruited during health checkups, and patients with CC recruited from outpatient clinics. Serum TMAO was measured using liquid chromatography-tandem mass spectrometry at baseline and at 4 and 12 weeks after treatment with magnesium oxide (MgO) or elobixibat (EXB). CC was classified as normal transit constipation (NTC) or slow-transit constipation (STC) by colonic transit time.

RESULTS

Overall, 72 HCs and 165 patients with CC (NTC, n = 110; STC, n = 55) were included. Mean serum TMAO levels were 1.8 (±1.1) µM and 9.0 (±8.1) µM in the HC and CC groups, respectively ( P < 0.01). Serum TMAO levels were significantly higher in the STC group than in the NTC group ( P < 0.01). Constipation treatment reduced serum TMAO levels to 5.5 ± 7.6 μM (n = 165, P < 0.01) at 4 weeks and 4.5 ± 7.6 μM (n = 165, P < 0.01) at 12 weeks. EXB lowered serum TMAO at 4 and 12 weeks in both NTC and STC. Conversely, MgO lowered TMAO only at 12 weeks in NTC and did not affect STC.

DISCUSSION: Constipation status, particularly STC, is associated with elevated serum TMAO levels. MgO or EXB significantly reduced serum TMAO, with a greater reduction observed with EXB.