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Next-generation probiotics as a therapeutic strategy for the treatment of phenylketonuria: a review.

Phenylketonuria (PKU) is a rare genetic disease that causes brain toxicity due to the inability of the body to convert dietary phenylalanine to tyrosine by the action of phenylalanine hydroxylase. The only treatment for PKU so far is lifelong dietary intervention to ensure normal human growth and neurodevelopment. However, in adults, low long-term adherence to this type of dietary intervention has been observed. Given the important role of the intestinal microbiota in the process of digestion and disease prevention, probiotics could be a therapeutic strategy to help degrade dietary phenylalanine, reducing its levels before ingestion. Genetically modified probiotics designed as live biotherapeutic agents for the treatment of specific diseases are sophisticated alternative therapeutic strategies. In this review, the focus is on demonstrating what has been elucidated so far about the use of next-generation probiotics as a therapeutic strategy in the treatment of individuals with PKU. The results described in the literature are encouraging and use genetically modified engineered probiotics showing efficacy both in vitro and in vivo. These probiotics appear to be suitable for meeting the unmet need for new drugs for PKU.