ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
A transgenic probiotic secreting a parasite immunomodulator for site-directed treatment of gut inflammation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.Nutrients · 2023Pooled it
- Microbial Biosensor for Sensing and Treatment of Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Engineered bacteria and bacterial derivatives as advanced therapeutics for inflammatory bowel disease.Essays in biochemistry · 2025Review
- Genetically engineered bacteria as inflammatory bowel disease therapeutics.Engineering microbiology · 2024Review
- Engineering probioticApplied and environmental microbiology · 2024Article
- Aggregation of adult parasitic nematodes in sex-mixed groups analysed by transient anomalous diffusion formalism.Journal of the Royal Society, Interface · 2024Article
- Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems forSynthetic and systems biotechnology · 2024Article
- Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development.Signal transduction and targeted therapy · 2023Review
- Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β,Discovery immunology · 2023Article
- Characterization of Eight Bacterial Biosensors for Microbial Diagnostic and Therapeutic Applications.ACS synthetic biology · 2022Article
- NAD(P)H fluorescence lifetime imaging of live intestinal nematodes reveals metabolic crosstalk between parasite and host.Scientific reports · 2022Article
- An engineered probiotic secreting Sj16 ameliorates colitis via Ruminococcaceae/butyrate/retinoic acid axis.Bioengineering & translational medicine · 2021Article
- Metabolomics-Guided Hypothesis Generation for Mechanisms of Intestinal Protection by Live Biotherapeutic Products.Biomolecules · 2021Article
- A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease.Journal of immunology research · 2021Article
- EngineeredExperimental and therapeutic medicine · 2020Review
- You Talking to Me? Says the Enteric Nervous System (ENS) to the Microbe. How Intestinal Microbes Interact with the ENS.Journal of clinical medicine · 2020Review
- Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders.Pathogens (Basel, Switzerland) · 2020Review
- Development of bacteria as diagnostics and therapeutics by genetic engineering.Journal of microbiology (Seoul, Korea) · 2019Review
- Neuronal impairment following chronic Toxoplasma gondii infection is aggravated by intestinal nematode challenge in an IFN-γ-dependent manner.Journal of neuroinflammation · 2019Article
- CRISPR-based curing and analysis of metabolic burden of cryptic plasmids inEngineering in life sciences · 2019Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New treatment strategies for inflammatory bowel disease are needed and parasitic nematode infections or application of helminth components improve clinical and experimental gut inflammation. We genetically modified the probiotic bacterium Escherichia coli Nissle 1917 to secrete the powerful nematode immunomodulator cystatin in the gut. This treatment was tested in a murine colitis model and on post-weaning intestinal inflammation in pigs, an outbred model with a gastrointestinal system similar to humans. Application of the transgenic probiotic significantly decreased intestinal inflammation in murine acute colitis, associated with increased frequencies of Foxp3(+) Tregs, suppressed local interleukin (IL)-6 and IL-17A production, decreased macrophage inflammatory protein-1α/β, monocyte chemoattractant protein -1/3, and regulated upon activation, normal T-cell expressed, and secreted expression and fewer inflammatory macrophages in the colon. High dosages of the transgenic probiotic were well tolerated by post-weaning piglets. Despite being recognized by T cells, secreted cystatin did not lead to changes in cytokine expression or macrophage activation in the colon. However, colon transepithelial resistance and barrier function were significantly improved in pigs receiving the transgenic probotic and post-weaning colon inflammation was reduced. Thus, the anti-inflammatory efficiency of a probiotic can be improved by a nematode-derived immunoregulatory transgene. This treatment regimen should be further investigated as a potential therapeutic option for inflammatory bowel disease.
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Registered trials
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.