Evidence map›Paper›PMID 33990606›Full record

ArticleNature communications2021

Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip.

M Tyler Nelson, Mark R Charbonneau, Heidi G Coia, Mary J Castillo, Corey Holt, Eric S Greenwood, Peter J Robinson, Elaine A Merrill, David Lubkowicz, Camilla A Mauzy

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

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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

10 authors.

M Tyler Nelson *United States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA. mark.nelson.35@us.af.mil.ORCID 0000-0002-7255-4964
Mark R Charbonneau *Synlogic Inc, Cambridge, MA, USA.ORCID 0000-0003-4893-8244
Heidi G CoiaUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.
Mary J CastilloSynlogic Inc, Cambridge, MA, USA.
Corey HoltUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.
Eric S GreenwoodUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.ORCID 0000-0002-4703-0405
Peter J RobinsonUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.
Elaine A MerrillUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.
David LubkowiczSynlogic Inc, Cambridge, MA, USA.
Camilla A MauzyUnited States Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioengineering Division, Wright-Patterson AFB, OH, Columbus, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Engineered bacteria (synthetic biotics) represent a new class of therapeutics that leverage the tools of synthetic biology. Translational testing strategies are required to predict synthetic biotic function in the human body. Gut-on-a-chip microfluidics technology presents an opportunity to characterize strain function within a simulated human gastrointestinal tract. Here, we apply a human gut-chip model and a synthetic biotic designed for the treatment of phenylketonuria to demonstrate dose-dependent production of a strain-specific biomarker, to describe human tissue responses to the engineered strain, and to show reduced blood phenylalanine accumulation after administration of the engineered strain. Lastly, we show how in vitro gut-chip models can be used to construct mechanistic models of strain activity and recapitulate the behavior of the engineered strain in a non-human primate model. These data demonstrate that gut-chip models, together with mechanistic models, provide a framework to predict the function of candidate strains in vivo.

Indexed as

Gastrointestinal MicrobiomeLab-On-A-Chip DevicesModels, BiologicalAnimalsBacteriaBiological TherapyCaco-2 CellsComputer SimulationEscherichia coliGenetic EngineeringHT29 CellsHumansIn Vitro TechniquesMicrofluidicsPhenylalaninePhenylketonuriasPhenylalanine

Identifiers

PMID33990606
PMCPMC8121789

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.