Hill Zoë R, Flynn Christina K, Adams James B
Barrett, The Honors College, Arizona State University, Tempe, AZ 85287, USA.
Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ 85287, USA.
Int J Mol Sci. 2024 Dec 3;25(23):12973. doi: 10.3390/ijms252312973.
Indoxyl sulfate-a bacterially derived metabolite-has been identified as a toxin that is elevated in children with autism spectrum disorder (ASD). As a neurotoxin, uremic toxin, nephrotoxin, cardiotoxin, osteotoxin, and myotoxin, indoxyl sulfate has been associated with several other conditions, including chronic kidney disease, acute kidney injury, Parkinson's disease, cognitive disorders, and mood disorders such as anxiety and depression. Indoxyl sulfate is derived from bacterial modification of host tryptophan, and elevated levels of indoxyl sulfate are associated with decreased levels of important neurotransmitters including serotonin, dopamine, and norepinephrine. This article will review what is currently known about indoxyl sulfate in relation to ASD and its comorbidities. A systematic review identified six studies of levels of indoxyl sulfate in children with ASD. All six studies found that indoxyl sulfate was significantly elevated in the urine of children with ASD compared to typically developing children. Through this review, indoxyl sulfate was identified as a toxic microbially derived metabolite that is significantly increased in a subset of children with ASD and may contribute to both core and co-morbid ASD symptoms.
硫酸吲哚酚——一种细菌衍生的代谢产物——已被确认为一种毒素，在自闭症谱系障碍（ASD）儿童中含量升高。作为一种神经毒素、尿毒症毒素、肾毒素、心脏毒素、骨毒素和肌肉毒素，硫酸吲哚酚还与其他几种病症有关，包括慢性肾病、急性肾损伤、帕金森病、认知障碍以及焦虑和抑郁等情绪障碍。硫酸吲哚酚源自宿主色氨酸的细菌修饰，硫酸吲哚酚水平升高与包括血清素、多巴胺和去甲肾上腺素在内的重要神经递质水平降低有关。本文将综述目前已知的关于硫酸吲哚酚与ASD及其合并症的关系。一项系统综述确定了六项关于ASD儿童硫酸吲哚酚水平的研究。所有六项研究均发现，与正常发育儿童相比，ASD儿童尿液中的硫酸吲哚酚显著升高。通过本次综述，硫酸吲哚酚被确定为一种有毒的微生物衍生代谢产物，在一部分ASD儿童中显著增加，可能导致ASD的核心症状和合并症状。
