The Adult Phenylketonuria (PKU) Gut Microbiome

Abstract

Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet that is frequently supplemented with an amino acid formula to maintain proper nutrition. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. In this study, we sequenced the V4 region of the 16S rRNA gene from stool samples collected from adults with PKU (n = 11) and non-PKU controls (n = 21). Gut bacterial communities were characterized through measurements of diversity and taxa abundance. Additionally, metabolic imputation was performed based on detected bacteria. Gut community diversity was lower in PKU individuals, though this effect was only statistically suggestive. A total of 65 genera across 5 phyla were statistically differentially abundant between PKU and control samples (p < 0.001). Additionally, we identified six metabolic pathways that differed between groups (p < 0.05), with four enriched in PKU samples and two in controls. While the child PKU gut microbiome has been previously investigated, this is the first study to explore the gut microbiome of adult PKU patients. We find that microbial diversity in PKU children differs from PKU adults and highlights the need for further studies to understand the effects of dietary restrictions.

Differences in faecal microbiome composition between adult patients with UCD and PKU and healthy control subjects

“…As the use of arginine and carnitine supplementation was associated with both differences in faecal microbiome as well as laxative use, the observed difference in microbiome composition may be due to collinearity. As reported previously [16] , [23] , [28] , the faecal microbiome of PKU patients differs from that of healthy control subjects. In this study we show for the first time a different faecal microbiome in UCD patients, compared to both PKU and healthy controls.…”

“…The increased abundance of Lachnospiracea was also seen in the faecal microbiome of pigs fed with a comparable diet to PKU patients: a low natural protein diet supplemented with amino acids [32] . Two studies with PKU patients reported opposite findings: both reported reduced prevalence of Lachnospiraceae [16] , [28] . In the study of Pinheiro de Oliveira [16] some patients used antibiotics (25% of the PKU group and 30% of the CON group used antibiotics in the 6 months preceding the faecal sample collection) and all patients were children.…”

“…Also the microbiome of children is different from adults [33] . The study by Mancilla [28] doesn't report antibiotic or other medication use. Both our study and these two studies were performed in small groups, with 8–10 patients per group, which can result in type 2 errors.…”

A low abundance of genus Bacteroides in gut microbiota is negatively correlated with blood phenylalanine levels in Uygur patients with phenylketonuria

“…Notably, a particularly divergent response in glucose and amino acid metabolism was observed between the affected and control groups. Unlike children with PKU, Mancilla et al (7) reported a significant differences in the abundance of specific bacterial groups in adult PKU patients. But the same was that both adults and children are involved in the abnormality of the glucose metabolism pathway.…”

Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism

“…( Pinheiro de Oliveira et al, 2016 ; Bassanini et al, 2019 ). Also in adult PKU patients, the gut microbiota, recently investigated by Mancilla et al (2021) , showed a similar pattern with an enrichment in Clostridium and a depletion in Faecalibacterium , but with a less pronounced abundance of Blautia spp.…”