Evidence map›Paper›PMID 33846627›Full record

ArticleNature microbiology2021

Gut-inhabiting Clostridia build human GPCR ligands by conjugating neurotransmitters with diet- and human-derived fatty acids.

Fang-Yuan Chang, Piro Siuti, Stephane Laurent, Thomas Williams, Emerson Glassey, Andreas W Sailer, David Benjamin Gordon, Horst Hemmerle, Christopher A Voigt

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. bioRxiv : the preprint server for biology · 2026
    Article
  12. Review
  13. Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. The microbiome diversifiesbioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Fang-Yuan ChangSynthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5819-6454
Piro SiutiSynthetic Biology Group, Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Stephane LaurentDisease Area X, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Thomas WilliamsThe Foundry, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3288-9513
Emerson GlasseySynthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Andreas W SailerDisease Area X, Novartis Institutes for BioMedical Research, Basel, Switzerland.ORCID http://orcid.org/0000-0002-9015-7946
David Benjamin GordonSynthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0619-7791
Horst HemmerleSynthetic Biology Group, Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Christopher A VoigtSynthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. cavoigt@gmail.com.ORCID http://orcid.org/0000-0003-0844-4776
Broad Institute · USNovartis (Switzerland) · CHMassachusetts Institute of Technology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human physiology is regulated by endogenous signalling compounds, including fatty acid amides (FAAs), chemical mimics of which are made by bacteria. The molecules produced by human-associated microbes are difficult to identify because they may only be made in a local niche or they require a substrate sourced from the host, diet or other microbes. We identified a set of uncharacterized gene clusters in metagenomics data from the human gut microbiome. These clusters were discovered to make FAAs by fusing exogenous fatty acids with amines. Using an in vitro assay, we tested their ability to incorporate 25 fatty acids and 53 amines known to be present in the human gut, from which the production of six FAAs was deduced (oleoyl dopamine, oleoyl tyramine, lauroyl tryptamine, oleoyl aminovaleric acid, α-linolenoyl phenylethylamine and caproyl tryptamine). These molecules were screened against panels of human G-protein-coupled receptors to deduce their putative human targets. Lauroyl tryptamine is found to be an antagonist to the immunomodulatory receptor EBI2 against its native oxysterol ligand (0.98 μM half-maximal inhibitory concentration), is produced in culture by Eubacterium rectale and is present in human faecal samples. FAAs produced by Clostridia may serve as a mechanism to modulate their host by mimicking human signalling molecules.

Indexed as

Gastrointestinal MicrobiomeAminesBacillotaDietFatty AcidsGastrointestinal TractHumansNeurotransmitter AgentsReceptors, G-Protein-CoupledSignal TransductionAminesFatty AcidsNeurotransmitter AgentsReceptors, G-Protein-Coupled

Identifiers

PMID33846627
OpenAlexW3155734097

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.