Evidence map›Paper›PMID 41017573›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

An Inflammation-Targeting Engineered Probiotic Escherichia coli Nissle 1917 with High Anti-TNF-α Nanobody Secretion Efficacy Alleviates Ulcerative Colitis.

Siqi Hua, Kaiqiang Li, Pengyou Shang, Lina Liu, Jiayu Pan, Bo Zhu, Zichun Hua

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. EngineeredFrontiers in immunology · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. Review
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

7 authors.

Siqi HuaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Kaiqiang LiSchool of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Pengyou ShangSchool of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Lina LiuState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, P. R. China.
Jiayu PanJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Bo ZhuSchool of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, P. R. China.ORCID https://orcid.org/0000-0001-6043-8774
Zichun HuaSchool of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, P. R. China.

Funding

Changzhou Municipal Department of Science and Technology CE20246001Changzhou Municipal Department of Science and Technology CJ20230017Changzhou Municipal Department of Science and Technology CJ20235009National Natural Science Foundation of China 32250016National Natural Science Foundation of China 82130106National Natural Science Foundation of China 82303774National Natural Science Foundation of China 82404501Natural Science Foundation of Jiangsu Province BE2023695Natural Science Foundation of Jiangsu Province BG2024026Natural Science Foundation of Jiangsu Province BK20230164Natural Science Foundation of Jiangsu Province BK20230165Natural Science Foundation of Jiangsu Province BK20231136Natural Science Foundation of Jiangsu Province BK20243001Natural Science Foundation of Jiangsu Province BY20241051
6 · The paper itself

Abstract

The probiotic Escherichia coli Nissle 1917 (EcN), clinically used for ulcerative colitis (UC) due to its safety and genetic tractability, exhibits limited therapeutic efficacy owing to poor targeting and colonization at inflamed sites. Phosphatidylserine (PS) exposure increases on apoptotic colon epithelial cells during UC progression, suggesting PS-targeting could enhance EcN localization. Here, EcN is engineered to surface-display Annexin A5 (ANXA5), a PS-binding protein, to improve inflammation targeting and colonization. Since TNF-α drives UC pathogenesis and anti-TNF-α biologics face cost and safety limitations, the secretion-hindering lpp gene is concurrently knocked out in ANXA5-expressing EcN, creating the inflammation-targeted, secretion-enhanced EcNΔlpp::A5. This base strain is further modified to secrete an anti-TNF-α nanobody (aTN), generating EcNΔlpp::A5-aTN. Both engineered strains demonstrate significantly stronger colonic colonization versus wild-type EcN, effectively attenuating oxidative stress-mediated epithelial apoptosis, restoring mucosal barriers, improving immune-microbiota balance, and alleviating murine colitis. EcNΔlpp::A5-aTN shows superior efficacy to EcNΔlpp::A5. This study develops an engineered EcN system with enhanced targeting, colonization, and secretion. By efficiently delivering anti-TNF-α nanobodies, EcNΔlpp::A5-aTN exhibits strong therapeutic potential for UC, overcoming limitations that hinder the clinical application of wild-type EcN.

Indexed as

Colitis, UlcerativeEscherichia coliInflammationProbioticsSingle-Domain AntibodiesTumor Necrosis Factor-alphaAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLSingle-Domain AntibodiesTumor Necrosis Factor-alphaannexin A5anti‐TNF‐α nanobodiesEscherichia coli Nissle 1917inflammatory bowel diseasetargeted drug delivery

Identifiers

PMID41017573
PMCPMC12697777

What OpenQuestion holds

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LicenceCC BY
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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.