Evidence map›Paper›PMID 35931082›Full record

ArticleCell2022

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Baylee J Russell, Steven D Brown, Nicole Siguenza, Irene Mai, Anand R Saran, Amulya Lingaraju, Erica S Maissy, Ana C Dantas Machado, Antonio F M Pinto, Concepcion Sanchez and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
17.7field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 131 citations in OpenAlex.

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  4. Genome-integrated engineering ofSynthetic and systems biotechnology · 2027
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26 more citing papers are in PubMed but not listed here.

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

20 authors at 2 institutions in 1 country.

Baylee J RussellDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Steven D BrownDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Nicole SiguenzaDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Irene MaiDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Anand R SaranDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Amulya LingarajuDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Erica S MaissyDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Ana C Dantas MachadoDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Antonio F M PintoClayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Concepcion SanchezDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Leigh-Ana RossittoDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Yukiko MiyamotoDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
R Alexander RichterDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Samuel B HoDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA; VA Health Sciences San Diego, La Jolla, CA 92161, USA.
Lars EckmannDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA.
Jeff HastyBioCircuits Institute, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
David J GonzalezDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
Alan SaghatelianClayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Rob KnightDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Amir ZarrinparDivision of Gastroenterology, University of California, San Diego, La Jolla, CA 92093, USA; VA Health Sciences San Diego, La Jolla, CA 92161, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: azarrinpar@ucsd.edu.
University of California, San Diego · USSalk Institute for Biological Studies · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Alan Saghatelian · 1985 to 2026
$82.8M
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
The Role of Altered Luminal Dynamics in OSA-Induced AtherosclerosisR01HL148801 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZARRINPAR, AMIR · 2019 to 2023
$4.0M
Rheumatic Diseases Research Training GrantT32AR064194 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GARY S FIRESTEIN, Monica Guma · 2013 to 2026
$3.8M
Engineering Native E. coli to Detect, Report, and Treat Colorectal CancerU01CA265719 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZARRINPAR, AMIR · 2021 to 2025
$3.1M
Obstructive sleep apnea, the microbiome and cardiovascular diseaseR01HL157445 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HADDAD, GABRIEL G · 2022 to 2025
$2.9M
Design and characterization of bacterial population dynamics in solid tumor modelsR01EB030134 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, TSIMRING, LEV S · 2021 to 2024
$2.5M
The Relationship of Gut Microbiome and Time Restricted Feeding in MetabolismK08DK102902 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZARRINPAR, AMIR · 2015 to 2019
$789k
BLRD VA I01 BX005707NCATS NIH HHS UL1 TR001442NCI NIH HHS P30 CA014195NCI NIH HHS R21 CA259921NCI NIH HHS U01 CA265719NHLBI NIH HHS R01 HL148801NHLBI NIH HHS R01 HL157445NIAAA NIH HHS P50 AA011999NIAMS NIH HHS T32 AR064194NIBIB NIH HHS R01 EB030134NICHD NIH HHS F31 HD106762NIDDK NIH HHS F32 DK113721NIDDK NIH HHS K08 DK102902NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R03 DK114536NIGMS NIH HHS T32 GM007752NIMH NIH HHS R21 MH117780
6 · The paper itself

Abstract

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.

Indexed as

Gastrointestinal MicrobiomeMicrobiotaAnimalsBacteriaEscherichia coliMiceTransgenesbile acid metabolismcomplex gut microbiomeglucose homeostasisgut microbiomemetabolismmicrobe-host intereractionsnon-model gut microbesprecision microbiome modulationsynthetic biologytype 2 diabetes

Identifiers

PMID35931082
PMCPMC9464905
OpenAlexW4289780991

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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.