Evidence map›Paper›PMID 34527515›Full record

ArticleMolecular genetics and metabolism reports2021

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

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics and metabolism reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Consumption of SolnulNutrients · 2023
    Trial
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

C TimmerDepartment of Dietetics and Nutritional science and Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
M DavidsDepartment of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
M NieuwdorpDepartment of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
J H M LevelsDepartment of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
J G LangendonkDepartment of Dietetics and Department of Internal Medicine, Center of Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands.
M BreederveldDepartment of Dietetics and Department of Internal Medicine, Center of Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands.
N Ahmadi MozafariDepartment of Dietetics and Department of Internal Medicine, Center of Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands.
M LangeveldDepartment of Dietetics and Nutritional science and Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Amsterdam University Medical Centers · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

16S rRNA, taxonomic marker genes, common to all bacteriaADI, Arginine Deimination. Bacteria derive energy from the deamination of arginine to citrulline and citrulline cleavage to ornithine plus carbamoyl phosphate. The latter is then converted into ATP and carbon dioxide, or used for pyrimidine biosynthesis. This route also generates two moles of ammonia (one from the arginine-citrulline conversion, the second from carbamoyl phosphate hydrolysis)Alpha Diversity, the species diversity in a microbial sample. Used to represent the taxonomic diversities of individual samplesAmmonium scavengers, agents developed for the reduction of blood ammonia concentration used for the treatment of patients with urea cycle disorders. Sodiumbenzoate and phenylbutyrate are ammonium scavengersARG1d, arginase 1 (ARG1) deficiencyASLd, argininosuccinate lyase (ASL) deficiencyASSd, argininosuccinate synthetase (ASS) deficiencyASV, Amplified Sequence Variant. A specific nucleotide sequence representing a bacterial lineageBCAA, branched chain amino acids: isoleucine, leucine and valineDEGs, differentially expressed genesDESeq, an R package to analyse count data from high-throughput sequencing assays such as RNA-Seq and test for differential expressionEAA supplement, essential amino acids supplement containing L-histidine, L-isoleucine, L-leucine, l-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptofaan and L-valine with optional L-cystine and L-tyrosine added (depending on what product is used)FaecalFPD, Faiths Phylogenetic Diversity, alpha diversity metric accounting for genetic diversityGenus, a taxonomic rankGutHyperammonemiaMetagenome, microbiome collective genomeMicrobiomeOTCd, ornithine transcarbamylase deficiencyPCoA, Principal Coordinate Analysis. PCoA is aimed at graphically representing a resemblance matrix between p elements (individuals, variables, objects, among others). By using PCoA we can visualize individual and/or group differences. Individual differences can be used to show outliersPFAA, precursor free amino acid supplement, in this case phenylalanine freePhenylketonuriaPKU, PhenylketonuriaProteolytic capacity, the capacity to break proteins down into smaller polypeptides or amino acids. In this study: enzymes involved in protein degradationRT-qPCR, real-time quantitative polymerase chain reactionSodium BPA, sodium phenylbutyrateUCD, urea cycle defectUrea cycle defect

Identifiers

PMID34527515
PMCPMC8433284
OpenAlexW3197572868

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.