Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Abstract

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome-gut-brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.

Keywords: ADHD; circadian rhythm; fatty acids; gastrointestinal microbiome; omega-3; probiotics.

Figure 1

Schematic diagram of the three pathways (nerve, neuroendocrine and immune) that configure the microbiome–gut–brain axis. CRH: corticotropin-releasing hormone; ACTH: adrenocorticotropic hormone; MC2-R: melanocortin receptor 2. CD4+ T cell: CD4-positive T cell.

Figure 2

Bacterial taxonomic classification including the genera cited in this article according to the National Center for Biotechnology Information (NCBI) Taxonomy Database [161,162].

Figure 3

Interaction between the gut microbiome and omega-3 PUFAs (polyunsaturated fatty acids), and effect on ADHD symptoms. The imbalance in the omega-3:omega-6 PUFA ratio leads to a state of neuroinflammation and a consequent disruption in the dopaminergic system (black arrows). Dopaminergic dysfunction is one of the main factors contributting to ADHD core symptoms. Alterations in the microbial composition have also been associated with ADHD symptoms, apparently via the influence of the gut microbiome on neurotransmission (microbiome–gut–brain axis (MGBA)). The administration of probiotics (green arrow) may boost the concentrations of omega-3 PUFAs. This would correct the omega-3:omega-6 imbalance and ultimately improve ADHD symptoms by stabilizing neuronal membranes, dopaminergic neurotransmission and reducing neuroinflammation. On the other hand, supplementation with eicosapentaenoic/docosahexanoic acids (EPA/DHA) (yellow arrow) could induce changes in the microbial composition that would be beneficial for ADHD symptoms, via dopaminergic neurotransmission regulation (MGBA).