Social epigenomics has emerged as an integrative field of research focused on identification of socio-environmental factors, their influence on human biology through epigenomic modifications, and how they contribute to current health disparities. Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g., DNA methylation, micro-RNA expression). Currently, research is focused on epigenetic changes in response to environment, as well as targeted epigenetic therapies and environmental/social strategies for potentially minimizing certain health disparities. Here, we will review recent findings in this field pertaining to conditions and diseases over life span encompassing prenatal to adult stages.

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.

The Pahenu2mutation in C57BL/6J mice is a well characterized model for studying phenylketonuria (PKU), with Pahenu2homozygotes displaying heightened blood phenylalanine and other characteristics of PKU. Pahenu2 homozygous females do not successfully rear young on any conventional diet due to their disease status. The most commonly used successful breeding strategy is crossing Pahenu2heterozygous females with homozygous mutant males; producing litters of 50% homozygous and 50% heterozygous animals. In many treatment studies the heterozygous pups produced are not useable, but add to experimental costs and total animals used. To this end our lab created a dietary regimen with reduced phenylalanine and increased large neutral amino acid content, enabling homozygous mating. Phenylalanine levels in homozygous females and males on the new diet are significantly lower than that of homozygous females and males on traditional diets (p = 1.35x10-4 and p = 1.5x10-5 respectively). Litters born to Pahenu2homozygous mothers on this diet demonstrate no significant difference in litter size compared to litters born to heterozygous mothers (p > 0.75). No observable defects were noted in litters born from homozygous crosses. This dietary regimen enables litter production of 100% Pahenu2homozygous animals for investigators who wish to rapidly expand their Pahenu2 mouse colony size or do not require heterozygous littermate controls in their PKU studies.