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.

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

“…The functional predictive analysis of PKU microbiota suggest how some bacterial functions were underrepresented with a potential influence on starch and sucrose metabolism, glycolysis/ gluconeogenesis, as well as biosynthesis of some amino acids, while the overrepresented taxa in PKU subjects were involved in LPS biosynthesis. The functional prediction seems to support the existing correlation between the dietary pattern in PKU, the gut microbiota composition, and the altered glucose metabolism, which in turn envisage a potential influence on the overweight status and obesity onset, promoted in a pro-inflammatory milieu (Verduci et al, 2020).…”

“…These taxa are considered among major butyrate-producing bacteria and a reduced production of butyrate is reported to be associated with the development of insulin resistance both in humans and in the animal model ( Qin et al, 2012 ; Karlsson et al, 2013 ). In PKU patients the different dietary pattern, focused on limiting Phe consumption, could be the cause of an unbalanced ratio Firmicutes/Bacteroidetes ( Verduci et al, 2020 ). The balance of these two phyla ratio has an important role for obesity and higher body mass index (BMI), since a decreased ratio is associated with an increase in energy harvest, resulting in weight gain ( Ley et al, 2005 ).…”

“…Several studies reported that BMI and childhood obesity are influenced by ratio Firmicutes/Bacteroidetes ( Indiani et al, 2018 ). Therefore, the modified microbiota of patients with PKU could potentially lead to a worse glycemic control, with a consequent insulin resistance, and weight gain ( Verduci et al, 2020 ).…”

Unveiling the Metabolic Effects of Glycomacropeptide

“…We know from the literature that plasma levels of trimethylamine N-oxide (TMAO), an active molecule generated by the gut microbiota, have been correlated with the risk of cardiovascular disease [ 36 ]. In PKU patients, the dysbiosis can be related to the underlying disease or the diet itself [ 37 ], but so far, the evidence is insufficient. These are important angles for further studies.…”

In Vitro Modulatory Effect of Stevioside, as a Partial Sugar Replacer in Sweeteners, on Human Child Microbiota

“…Current research aims to assess the effects of increased sugar consumption in products considered to be dietary [ 14 , 15 ]. Thus, some data indicate adverse effects, such as loss of intestinal motility, stimulation of inflammatory processes, or cancer risk [ 5 ].…”