Evidence map›Paper›PMID 33934200›Full record

ArticleEuropean journal of nutrition2021

The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, L-carnitine and related precursors by the human gut microbiota.

Priscilla Day-Walsh, Emad Shehata, Shikha Saha, George M Savva, Barbora Nemeckova, Jasmine Speranza, Lee Kellingray, Arjan Narbad, Paul A Kroon

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in European journal of nutrition, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02653001 (Stool Sample Collection for Research Using the In-vitro QIB Colon Model), which is not on this map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% 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.

NCT02653001 naenrolling by invitationnot on this map

Stool Sample Collection for Research Using the In-vitro QIB Colon Model

TypeinterventionalSponsorQuadram Institute BioscienceRan2015 to 2030Enrolled20ConditionsHuman Gut MicrobiotaArmsStool sample collection
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Gut microbes · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

9 authors at 2 institutions in 3 countries.

Priscilla Day-WalshQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Emad ShehataQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Shikha SahaQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
George M SavvaQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Barbora NemeckovaQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Jasmine SperanzaQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Lee KellingrayQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Arjan NarbadQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
Paul A KroonQuadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK. paul.kroon@quadram.ac.uk.ORCID http://orcid.org/0000-0002-9805-6947
Norwich Research Park · GBUniversity of Messina · IT

Funding

Biotechnology and Biological Sciences Research Council BB/CCG1860/1.Biotechnology and Biological Sciences Research Council BBS/E/F/00042220Biotechnology and Biological Sciences Research Council BBS/E/F/00042241Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10343Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10346Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10347Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10356Biotechnology and Biological Sciences Research Council BBS/OS/GC/000010BBiotechnology and Biological Sciences Research Council Grant No. BB/J004545/1
6 · The paper itself

Abstract

purposePlasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon.

methodsTMA production from choline, L-carnitine, betaine and γ-butyrobetaine was studied over 24-48 h using an in-vitro human colon model with metabolite quantification performed using LC-MS.

resultsCholine was metabolised via the direct choline TMA-lyase route but not the indirect choline-betaine-TMA route, conversion of L-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for L-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA.

conclusionThe metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. TRIAL REGISTRATION NUMBER: NCT02653001 ( http://www.clinicaltrials.gov ), registered 12 Jan 2016.

Indexed as

Gastrointestinal MicrobiomeAnimalsCarnitineCholineColonFermentationHumansMethylaminesCarnitineCholineMethylaminestrimethylamineBetaineCardiovascular diseaseCarnitineFish odour syndromeHuman gut microbiotaLecithinMetabolic diseasePhosphatidylcholineTMAOγ-Butyrobetaine

Identifiers

PMID33934200
PMCPMC8437865
OpenAlexW3158847163

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.