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

三甲氨基尿症(TMAU)是一种疾病，受影响的人会有严重的体味，通常伴随着严重的口臭。这种疾病是由一种名为FMO3的基因突变引起的，而不是因为糟糕的卫生条件。为什么FMO3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时(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)，那么生活在我们肠道中的细菌就会引起问题。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一种化学物质，也是给腐烂的鱼带来特有气味的化学物质。对于FMO3基因正常的人来说，没有气味问题，因为我们肝脏中的FMO3酶将三甲胺转化为一种无味的化学物质。但是，如果FMO3酶不能做到这一点，那么三甲胺就不会改变，而是从尿液、汗液和呼吸中排泄出来。患有TMAU的人会经历社会孤立、嘲笑和就业前景有限，这通常意味着生活质量较低；在这一人群中，抑郁、自杀和离婚的发生率很高。我们的研究将测试一种治疗TMAU的方法，它将减少尿中三甲胺的排泄量。我们的临床前发现将为未来的人类临床研究铺平道路。身体和呼吸气味的减少将极大地有助于改善TMAU患者的生活质量。

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.