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May 2, 20260 citations

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

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YIYo IshiharaEIEikichi IharaHOHidenori Ohkubo

Key Result

Chronic constipation was associated with higher mean serum TMAO levels compared to healthy controls (9.0 vs 1.8 µM; p<0.01), which significantly decreased to 4.5 µM after 12 weeks of treatment.

Key Points

  • This study aims to investigate the impact of chronic constipation on serum TMAO levels and determine how treatment affects these levels.
  • Multicenter observational study conducted from July 2023 to September 2024 at three Japanese centers.
  • Participants included 165 patients with chronic constipation and 72 healthy controls.
  • Serum TMAO levels measured at baseline, 4 weeks, and 12 weeks after treatment with magnesium oxide or elobixibat.
  • Mean serum TMAO levels were significantly higher in CC (9.0 ± 8.1 µM) than in HCs (1.8 ± 1.1 µM, p<0.01).
  • Serum TMAO levels significantly dropped to 5.5 ± 7.6 µM at 4 weeks and 4.5 ± 7.6 µM at 12 weeks after treatment (n=165, p<0.01).
  • Elobixibat demonstrated a greater reduction in TMAO levels compared to magnesium oxide.

Study Design

Type

Observational (n=237)

Multicenter

Yes

Structured PICO

Does treatment with magnesium oxide or elobixibat reduce serum TMAO levels in patients with chronic constipation?

P
Population
237 participants including 72 healthy controls and 165 patients with chronic constipation (110 normal transit constipation, 55 slow-transit constipation) from three Japanese centers.
I
Intervention
Treatment with magnesium oxide (MgO) or elobixibat for 12 weeks
C
Comparator
Healthy controls (for baseline comparison) and pre-treatment baseline levels
O
Outcome
Serum TMAO levels at baseline, 4 weeks, and 12 weekssurrogate

Chronic constipation is associated with elevated serum TMAO, a cardiovascular risk marker, which can be significantly reduced with laxative treatments like elobixibat or magnesium oxide.

Main Result

Absolute Event Rate: 9% vs 1.8%

p-value: p=<0.01

Abstract

BACKGROUND: 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 prospective observational study (July 2023-September 2024), conducted at three 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. 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 4weeks and 4.5 ± 7.6 µM (n = 165, p<0.01) at 12 weeks. Elobixibat 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. CONCLUSIONS: Constipation status, particularly STC, is associated with elevated serum TMAO levels. MgO or elobixibat significantly reduced serum TMAO, with a greater reduction observed with elobixibat.

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Cite This Study

Ishihara et al. (2026) conducted an observational in Chronic constipation (n=237). Magnesium oxide or elobixibat vs. Healthy controls (baseline) / Pre-treatment (follow-up) was evaluated on Mean serum TMAO levels (p=<0.01). Chronic constipation was associated with higher mean serum TMAO levels compared to healthy controls (9.0 vs 1.8 µM; p<0.01), which significantly decreased to 4.5 µM after 12 weeks of treatment.

synapsesocial.com/papers/69f594e171405d493afffcefhttps://doi.org/10.14309/ctg.0000000000001046
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