Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review

Abstract

The composition and functioning of the gut microbiota, the complex population of microorganisms residing in the intestine, is strongly affected by endogenous and exogenous factors, among which diet is key. Important perturbations of the microbiota have been observed to contribute to disease risk, as in the case of neurological disorders, inflammatory bowel disease, obesity, diabetes, cardiovascular disease, among others. Although mechanisms are not fully clarified, nutrients interacting with the microbiota are thought to affect host metabolism, immune response or disrupt the protective functions of the intestinal barrier. Similarly, key intermediaries, whose presence may be strongly influenced by dietary habits, sustain the communication along the gut-brain-axis, influencing brain functions in the same way as the brain influences gut activity. Due to the role of diet in the modulation of the microbiota, its composition is of high interest in inherited errors of metabolism (IEMs) and may reveal an appealing therapeutic target. In IEMs, for example in phenylketonuria (PKU), since part of the therapeutic intervention is based on chronic or life-long tailored dietetic regimens, important variations of the microbial diversity or relative abundance have been observed. A holistic approach, including a healthy composition of the microbiota, is recommended to modulate host metabolism and affected neurological functions.

Keywords: anxiety; depression; diet; immune response; inherited errors of metabolism; microbial; neurological function; nutrients.

Figure 1

Microbial role in the bidirectional communication between brain and gut. SCFAs: short-chain fatty acids; BCFAs: branched-chain fatty acids.

Figure 2

Microbial signature in health and disease and its impact on gastrointestinal homeostasis. Up and down arrows indicate increase and decrease, respectively. TJ = tight junction.

Figure 3

Modulation of dietary approach in PKU. The provision of low-protein foods that are balanced in their content and the quality of carbohydrates may favour patients with PKU in better controlling the composition of the microbiota and as a consequence the host metabolism connected to microbial metabolic processes. Phe-free AAs are the mainstay of the dietary approach to PKU and their integration in a dietary regimen poor of natural proteins needed to reduce the intake of Phe is key to patient wellbeing. New options with AAs deriving from natural sources or specifically engineered to provide absorption features closer to intact proteins are available for patients with PKU. A different way of administering AAs could prove favourable for patient with PKU by modulating some of the imbalances typical of the PKU diet.