Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases causing hyperammonemic encephalopathy. Despite intensive dietary and pharmacological therapy, outcome is poor in a subset of UCD patients. Reducing ammonia production by changing faecal microbiome in UCD is an attractive treatment approach. We compared faecal microbiome composition of 10 UCD patients, 10 healthy control subjects and 10 phenylketonuria (PKU) patients. PKU patients on a low protein diet were included to differentiate between the effect of a low protein diet and the UCD itself on microbial composition. Participants were asked to collect a faecal sample and to fill out a 24 h dietary journal. DNA was extracted from faecal material, taxonomy was assigned and microbiome data was analyzed, with a focus on microbiota involved in ammonia metabolism.

In this study we show an altered faecal microbiome in UCD patients, different from both PKU and healthy controls. UCD patients on dietary and pharmacological treatment had a less diverse faecal microbiome, and the faecal microbiome of PKU patients on a protein restricted diet with amino acid supplementation showed reduced richness compared to healthy adults without a specific diet. The differences in the microbiome composition of UCD patients compared to healthy controls were in part related to lactulose use. Other genomic process encodings involved in ammonia metabolism, did not seem to differ. Since manipulation of the microbiome is possible, this could be a potential treatment modality. We propose as a first next step, to study the impact of these faecal microbiome alterations on metabolic stability.

Take home message

The faecal microbiome of UCD patients was less diverse compared to PKU patients and even more compared to healthy controls.

中文翻译：

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成年 UCD 和 PKU 患者与健康对照受试者粪便微生物组成的差异

尿素循环障碍（UCD）是一组引起高氨性脑病的罕见遗传代谢性疾病。尽管进行了强化饮食和药物治疗，部分 UCD 患者的治疗结果仍很差。通过改变UCD的粪便微生物组来减少氨的产生是一种有吸引力的治疗方法。我们比较了 10 名 UCD 患者、10 名健康对照受试者和 10 名苯丙酮尿症 (PKU) 患者的粪便微生物组成。纳入低蛋白饮食的 PKU 患者是为了区分低蛋白饮食和 UCD 本身对微生物组成的影响。参与者被要求收集粪便样本并填写 24 小时饮食日记。从粪便中提取 DNA，进行分类并分析微生物组数据，重点关注参与氨代谢的微生物群。

在这项研究中，我们展示了 UCD 患者粪便微生物组的改变，与 PKU 和健康对照者不同。接受饮食和药物治疗的 UCD 患者的粪便微生物组多样性较低，与没有特定饮食的健康成年人相比，接受蛋白质限制饮食并补充氨基酸的 PKU 患者的粪便微生物组丰富度有所降低。UCD 患者与健康对照者微生物组组成的差异部分与乳果糖的使用有关。参与氨代谢的其他基因组过程编码似乎没有不同。由于操纵微生物组是可能的，这可能是一种潜在的治疗方式。我们建议下一步第一步是研究这些粪便微生物组的变化对代谢稳定性的影响。

带回家留言

与 PKU 患者相比，UCD 患者的粪便微生物群多样性较低，与健康对照相比，多样性甚至更高。