Differences in faecal microbiome composition between adult patients with UCD and PKU and healthy control subjects

C. Timmer*, M. Davids, M. Nieuwdorp, J.H.M. Levels, J. G. Langendonk, M. Breederveld, N. Ahmadi Mozafari, M. Langeveld

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number100794
JournalMolecular Genetics and Metabolism Reports
Volume29
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This study was supported by ESN , the Dutch Society for Inborn Errors of Metabolism . M.N. is supported by a personal ZONMW VICI grant 2020 [ 09150182010020 ].

Publisher Copyright:
© 2021 The Authors

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