Systematic Review and Meta-Analysis of Dietary Interventions and Microbiome in Phenylketonuria

Abstract

Inborn errors of metabolism (IEMs) comprise a diverse group of monogenic disorders caused by enzyme deficiencies that result either in a toxic accumulation of metabolic intermediates or a shortage of essential end-products. Certain IEMs, like phenylketonuria (PKU), necessitate stringent dietary intervention that could lead to microbiome dysbiosis, thereby exacerbating the clinical phenotype. The objective of this systematic review was to examine the impact of PKU therapies on the intestinal microbiota. This research was conducted following the PRISMA Statement, with data from PubMed, Scopus, ScienceDirect, and Web of Science. A total of 18 articles meeting the inclusion criteria were published from 2011 to 2022. Significant reductions in several taxonomic groups in individuals with PKU when compared to the control group were detected in a quantitative analysis conducted across seven studies. The meta-analysis synthesis indicates a contrast in biodiversity between PKU subjects and the control population. Additionally, the meta-regression results, derived from the Bacillota/Bacteroidota ratio data, suggest a potential influence of diet in adult PKU populations (p = 0.004). It is worth noting that the limited number of studies calls for further research and analysis in this area. Our findings indicate the necessity of enhancing understanding of microbiota variability in reaction to treatments among PKU subjects to design tailored therapeutic and nutritional interventions to prevent complications resulting from microbiota disruption.

Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison

“…Moreover, focusing on fibre intake, even though children with PKU consume more vegetables and fibre, especially soluble fibre, their gut microbiota composition is not favourable, with important alterations in Firmicutes phylum and a reduction in butyrate-producing genera [17,18]. A recent systematic review and meta-analysis examining PKU microbiota [19] highlighted the impact of diet in PKU, together with the administration of PSs and/or other supplementations, on the alterations in microbial communities, potentially influencing not only carbohydrate metabolism but also AA biosynthesis and gastroenterological symptomatology. At present, no data are available on the GI and GL of PSs for PKU, but the intake of Phe-free amino acids has been shown to cause a significantly higher insulin peak after the intake of Phe-free L-AA PSs in both humans and rats [20].…”