MICA: Therapy for the body and breath malodour disorder Trimethylaminuria (TMAU)

MICA：治疗身体和呼吸异味障碍三甲胺尿 (TMAU)

• 批准号: MR/K015494/1
• 负责人: Elizabeth Shephard
• 金额: $ 45.96万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015494%2F1
• 关键词: MICA; Therapy; body; breath; malodour

Trimethylaminuria (TMAU) is a disorder in which affected people suffer from severe body odour often accompanied by severe bad breath. The disorder arises because of mutations in a gene called FMO3 and not because of poor hygiene. Why do changes in the FMO3 gene cause body and breath odour? When we eat food that contains choline (which many foods do, e.g. red meat, seafood, some vegetables, soya, eggs and chocolate) then the bacteria that live in our gut cause the problem. The bacteria break choline down to produce a small molecule called trimethylamine. This chemical is the one to which the human nose is most sensitive and which is also the chemical that gives rotting fish its characteristic smell. In people with a normal FMO3 gene there is no odour problem because the FMO3 enzyme we have in our liver changes trimethylamine into a chemical that does not smell. BUT, if the FMO3 enzyme cannot do this, then the trimethylamine is not changed and is excreted in urine, sweat and breath. Social isolation, ridicule and limited employment prospects are experienced by those with TMAU, this usually means a low quality of life; high levels of depression, suicide and divorce occur in this population. Our study will test a therapy for TMAU that will reduce the amount of urinary trimethylamine excreted. Our pre-clinical findings will prepare the way for clinical studies in humans in the future. A reduction in body and breath odour will contribute greatly to an improved quality of life for those with TMAU.

三甲基氨基尿症（TMAU）是一种疾病，其中受影响的人患有严重的体臭，通常伴有严重的口臭。这种疾病的发生是因为一种叫做FMO 3的基因突变，而不是因为卫生条件差。为什么FMO 3基因的变化会导致身体和呼吸气味？当我们吃含有胆碱的食物（许多食物都含有胆碱，例如红肉，海鲜，一些蔬菜，大豆，鸡蛋和巧克力）时，生活在我们肠道中的细菌就会引起问题。这种细菌分解胆碱产生一种叫做三甲胺的小分子。这种化学物质是人类鼻子最敏感的化学物质，也是使腐烂的鱼具有其特有气味的化学物质。在正常FMO 3基因的人中，没有气味问题，因为我们肝脏中的FMO 3酶将三甲胺转化为没有气味的化学物质。但是，如果FMO 3酶不能做到这一点，那么三甲胺不会改变，并通过尿液，汗液和呼吸排出体外。社会孤立，嘲笑和有限的就业前景所经历的那些与TMAU，这通常意味着低生活质量;高水平的抑郁症，自杀和离婚发生在这个人群。我们的研究将测试一种治疗TMAU的方法，该方法将减少尿中三甲胺的排泄量。我们的临床前研究结果将为未来的人类临床研究铺平道路。减少身体和呼吸气味将大大有助于改善TMAU患者的生活质量。

项目成果

Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis.

• DOI: 10.1124/dmd.117.077636
• 发表时间: 2018-01
• 期刊: Drug metabolism and disposition: the biological fate of chemicals
• 作者: Veeravalli S;Karu K;Scott F;Fennema D;Phillips IR;Shephard EA
• 通讯作者: Shephard EA

Clinical utility gene card for: Trimethylaminuria - update 2014.

• DOI: 10.1038/ejhg.2014.226
• 发表时间: 2015-09
• 期刊: European journal of human genetics : EJHG
• 作者: Shephard EA;Treacy EP;Phillips IR
• 通讯作者: Phillips IR

A highly sensitive liquid chromatography electrospray ionization mass spectrometry method for quantification of TMA, TMAO and creatinine in mouse urine.

• DOI: 10.1016/j.mex.2017.09.004
• 发表时间: 2017
• 期刊: MethodsX
• 影响因子: 1.9
• 作者: Veeravalli S;Karu K;Phillips IR;Shephard EA
• 通讯作者: Shephard EA

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease.

• DOI: 10.1124/dmd.116.070615
• 发表时间: 2016-11
• 期刊: Drug metabolism and disposition: the biological fate of chemicals
• 作者: Fennema D;Phillips IR;Shephard EA
• 通讯作者: Shephard EA