Evidence map›Paper›PMID 34480146›Full record

ArticleCellular & molecular immunology2021

Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis.

Xu Yan, Xin-Yi Liu, Dian Zhang, Yu-Dian Zhang, Zi-Hua Li, Xu Liu, Fuqing Wu, Guo-Qiang Chen

Open access · bronzeAbstract read
In one paragraph

Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
10.4field-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

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
    Pooled it
  2. Pooled it
  3. Genome-integrated engineering ofSynthetic and systems biotechnology · 2027
    Article
  4. Article
  5. Review
  6. Metabolic Engineering of ProbioticFoods (Basel, Switzerland) · 2026
    Article
  7. Article
  8. Targeted and quantitatively modeled biologic delivery via dual-functional probiotic yeast in inflammatory bowel disease.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. International journal of molecular sciences · 2026
    Article
  18. Current and emerging approaches to manage chronic inflammatory gut disorders.Frontiers in cellular and infection microbiology · 2026
    Review
  19. An Efficient COAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Review

23 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

8 authors at 1 institution in 1 country.

Xu YanCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Xin-Yi LiuCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Dian ZhangCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Yu-Dian ZhangCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Zi-Hua LiCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Xu LiuCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Fuqing WuCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
Guo-Qiang ChenCenter for Synthetic and Systems Biology, Tsinghua University, Beijing, China. chengq@mail.tsinghua.edu.cn.ORCID http://orcid.org/0000-0002-7226-1782
Tsinghua University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 21761132013National Natural Science Foundation of China (National Science Foundation of China) 31771886National Natural Science Foundation of China (National Science Foundation of China) 31870859National Natural Science Foundation of China (National Science Foundation of China) 31971170Tsinghua University (THU) 2020Z99CFG002
6 · The paper itself

Abstract

Colitis is a common disease of the colon that is very difficult to treat. Probiotic bacteria could be an effective treatment. The probiotic Escherichia coli Nissle 1917 (EcN) was engineered to synthesize the ketone body (R)-3-hydroxybutyrate (3HB) for sustainable production in the gut lumen of mice suffering from colitis. Components of heterologous 3HB synthesis routes were constructed, expressed, optimized, and inserted into the EcN genome, combined with deletions in competitive branch pathways. The genome-engineered EcN produced the highest 3HB level of 0.6 g/L under microaerobic conditions. The live therapeutic was found to colonize the mouse gastrointestinal tract over 14 days, elevating gut 3HB and short-chain-length fatty acid (SCFA) levels 8.7- and 3.1-fold compared to those of wild-type EcN, respectively. The sustainable presence of 3HB in mouse guts promoted the growth of probiotic bacteria, especially Akkermansia spp., to over 31% from the initial 2% of all the microbiome. As a result, the engineered EcN termed EcNL4 ameliorated colitis induced via dextran sulfate sodium (DSS) in mice. Compared to wild-type EcN or oral administration of 3HB, oral EcNL4 uptake demonstrated better effects on mouse weights, colon lengths, occult blood levels, gut tissue myeloperoxidase activity and proinflammatory cytokine concentrations. Thus, a promising live bacterium was developed to improve colonic microenvironments and further treat colitis. This proof-of-concept design can be employed to treat other diseases of the colon.

Indexed as

ColitisEscherichia coli InfectionsProbiotics3-Hydroxybutyric AcidAnimalsEscherichia coliMice3-Hydroxybutyric Acid3HBColitisColonic microenvironmentEscherichia coli Nissle 1917Metabolic engineeringMicrobiomesProbioticsSynthetic biologyβ-hydroxybutyrate

Identifiers

PMID34480146
PMCPMC8484604
OpenAlexW3196320527

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.