Gabriele Stefano, Sacco Roberto, Altieri Laura, Neri Cristina, Urbani Andrea, Bravaccio Carmela, Riccio Maria Pia, Iovene Maria Rosaria, Bombace Francesca, De Magistris Laura, Persico Antonio M
Unit of Child and Adolescent NeuroPsychiatry, University Campus Bio-Medico, Rome, Italy.
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
Autism Res. 2016 Jul;9(7):752-9. doi: 10.1002/aur.1571. Epub 2015 Oct 6.
The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
尿毒症毒素对甲酚（4-甲基苯酚）要么来源于环境，要么可由存在于肠腔中的产甲酚细菌从酪氨酸合成。此前在8岁以下的意大利和法国自闭症谱系障碍（ASD）儿童尿液中发现对甲酚含量升高，且可能与自闭症严重程度或异常行为强度有关。本研究旨在探究ASD患者尿液中对甲酚升高的产生机制。因此，采用高效液相色谱法对53名意大利ASD儿童样本中的尿液对甲酚水平进行了测量，这些儿童接受了以下评估：（a）通过体外粪便检测评估肠道中梭菌属菌株的存在情况以及粪便中艰难梭菌衍生毒素A/B的情况；（b）使用乳果糖/甘露醇（LA/MA）试验评估肠道通透性；（c）评估出生后前2年因反复感染而频繁使用抗生素的情况；（d）使用布里斯托大便分类法评估大便习惯。慢性便秘是与总尿对甲酚浓度显著相关的唯一变量（P < 0.05）。未发现与肠道菌群中梭菌属的存在（P = = 0.92）、肠道通透性增加（P = = 0.18）或婴儿早期频繁使用抗生素（P = = 0.47）有关。未发现ASD儿童肠道中携带艰难梭菌或粪便中释放毒素A/B。总之，肠道转运时间延长和慢性便秘的ASD幼儿尿液中对甲酚水平升高。《自闭症研究》2016年，9: 752 - 759。© 2015国际自闭症研究协会，威利期刊公司
