Haarhuis Julia E, Day-Walsh Priscilla, Shehata Emad, Savva George M, Peck Barbora, Philo Mark, Kroon Paul A
Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Robinson Way, Cambridge, UK.
Mol Nutr Food Res. 2025 Jun 29:e70166. doi: 10.1002/mnfr.70166.
High circulating levels of trimethylamine N-oxide (TMAO) are linked to metabolic diseases, adverse outcomes after heart failure, and atherogenic effects in animal models and in human subjects. l-Carnitine and choline are major dietary precursors of TMAO. These are first converted to trimethylamine (TMA) by gut microbiota, which is absorbed by the host and converted into TMAO by hepatic flavin-containing monooxygenases (FMOs). The minimal absorption of pomegranate polyphenols by the host suggests that they may reach the colon for further metabolism by the gut microbiome. This study investigates the ability of a polyphenol-rich pomegranate extract to inhibit TMA production by human fecal microbiota. Batch fermentations were conducted with 1% human fecal inoculum, l-carnitine, or choline, and a pomegranate extract (anaerobic, pH 6.6-7.1, 37°C) for 24 or 48 h. Methylamines were quantified using LC-MS/MS with isotopically labeled internal standards. The pomegranate extract significantly delayed and reduced the rate of TMA production from both choline and l-carnitine. The effect was dose-dependent for l-carnitine, with the highest dose delaying the average midpoint of l-carnitine metabolism by 16 h (95% CI = 8.4-24; p = 0.001). The pomegranate extract significantly reduced TMA production from choline and l-carnitine in vitro.
血液中高水平的氧化三甲胺（TMAO）与代谢性疾病、心力衰竭后的不良后果以及动物模型和人类受试者中的致动脉粥样硬化作用有关。左旋肉碱和胆碱是TMAO的主要饮食前体。它们首先被肠道微生物群转化为三甲胺（TMA），TMA被宿主吸收并由肝脏含黄素单加氧酶（FMO）转化为TMAO。宿主对石榴多酚的吸收极少，这表明它们可能到达结肠，由肠道微生物群进行进一步代谢。本研究调查了富含多酚的石榴提取物抑制人类粪便微生物群产生TMA的能力。使用1%的人类粪便接种物、左旋肉碱或胆碱以及石榴提取物进行分批发酵（厌氧，pH 6.6 - 7.1，37°C），持续24或48小时。使用带有同位素标记内标的液相色谱 - 串联质谱法对甲胺进行定量。石榴提取物显著延迟并降低了胆碱和左旋肉碱产生TMA的速率。对于左旋肉碱，这种作用呈剂量依赖性，最高剂量使左旋肉碱代谢的平均中点延迟了16小时（95%置信区间 = 8.4 - 24；p = 0.001）。石榴提取物在体外显著降低了胆碱和左旋肉碱产生的TMA。
