ArticlePloS one2017
Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 77 citations in OpenAlex.
- Advances and perspectives in genetically encoded biosensors for biomarker detection and theranostic circuits.Synthetic and systems biotechnology · 2027Review
- Engineering commensal microbes for host health.Cell host & microbe · 2026Review
- Engineered probiotic ameliorates hyperlipidemia and atherosclerosis by secreting PCSK9 nanobodies and regulating gut microbiota.Bioengineering & translational medicine · 2025Article
- Metabolic engineering of Lactobacilli spp. for disease treatment.Microbial cell factories · 2025Review
- Potential applications of engineered bacteria in disease diagnosis and treatment.Microbiome research reports · 2025Review
- Targeted delivery of the probiotic Saccharomyces boulardii to the extracellular matrix enhances gut residence time and recovery in murine colitis.Nature communications · 2024Article
- Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review.Preventive nutrition and food science · 2024Review
- Genetically Engineered Microorganisms and Their Impact on Human Health.International journal of clinical practice · 2024Review
- Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms.Nature biotechnology · 2023Article
- Recent advances in genetic tools for engineering probiotic lactic acid bacteria.Bioscience reports · 2023Article
- Expression of phenylalanine ammonia lyase as an intracellularly free and extracellularly cell surface-immobilized enzyme on a gut microbe as a live biotherapeutic for phenylketonuria.Science China. Life sciences · 2023Article
- Biotechnological Applications of Probiotics: A Multifarious Weapon to Disease and Metabolic Abnormality.Probiotics and antimicrobial proteins · 2022Review
- Gastrointestinal Microbiota and Their Manipulation for Improved Growth and Performance in Chickens.Foods (Basel, Switzerland) · 2022Review
- Engineered probiotics.Microbial cell factories · 2022Review
- The Adult Phenylketonuria (PKU) Gut Microbiome.Microorganisms · 2021Article
- Angiotensin (1-7) Expressing Probiotic as a Potential Treatment for Dementia.Frontiers in aging · 2021Article
- Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review.Nutrients · 2020Review
- Biosensing in Smart Engineered Probiotics.Biotechnology journal · 2020Review
- The Microbiome as a Therapeutic Target for Multiple Sclerosis: Can Genetically Engineered Probiotics Treat the Disease?Diseases (Basel, Switzerland) · 2020Review
- Engineering probiotics as living diagnostics and therapeutics for improving human health.Microbial cell factories · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.
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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.