Gut microbiota and attention deficit hyperactivity disorder: new perspectives for a challenging condition

Abstract

A bidirectional communication between the gut and the brain (gut-brain axis) is well recognized with the gut microbiota viewed as a key regulator of this cross-talk. Currently, a body of preclinical and to a lesser extent epidemiological evidence supports the notion that host-microbe interactions play a key role in brain development and function and in the etiology of neurodevelopmental disorders. Early life events and shifts away from traditional lifestyles are known to impact gut microbiota composition and function and, thereby, may increase the risk of developing neurodevelopmental disorders. Attention deficit hyperactivity disorder (ADHD) is nowadays the most prevalent neurodevelopmental disorder. Despite many years of research its etiology is unclear and its diagnosis and treatment are still challenging. Different factors reported to be associated with the risk of developing ADHD and/or linked to different ADHD manifestations have also been linked to shifts in gut microbiota composition, suggesting a link between the microbiota and the disorder. Evidence from preliminary human studies also suggests that dietary components that modulate gut microbiota may also influence ADHD development or symptoms, although further studies are warranted to confirm this hypothesis. Here, we firstly review the potential mechanisms by which the gut microbiota may regulate the brain-gut axis and influence behavior and neurodevelopmental disorders. Secondly, we discuss the current knowledge about the different factors and dietary components reported to be associated with the risk of developing ADHD or its manifestations and with shifts in gut microbiota composition. Finally, we briefly highlight the need to progress our understanding regarding the role of the gut microbiota in ADHD, since this could open new avenues for early intervention and improved management of the disease.

The Potential Influence of the Microbiome on the Development and Progression of ADHD

“…This can in turn, decrease the permeability of the BBB, which can lead to inflammation of brain parenchyma [100]. Severe dysbiosis has been associated with chronic inflammatory intestinal disorders and psychiatric illnesses such as schizophrenia, anxiety, depression [98] and ADHD [90,101]. A systematic review supports the later findings concluding that patients with ADHD have increased levels of inflammatory cytokines [102].…”

“…Also, these products decrease the amount of pro-inflammatory IFN gamma in comparison to the anti-inflammatory IL-10 [87]. In contrast, QA stimulates microglial cells and increases the ratio of IFN gamma/IL-10 [87], resulting in proinflammatory effects [90]. Although KA shows neuroprotective properties, human and animal studies show that high levels of KA are associated with cognitive abnormalities such as attention and memory issues typically associated with psychiatric disease [91,92].…”

“…The influence of probiotic strains on psychiatric diseases has been examined by multiple studies, concluding a positive effect on such illnesses and are thus described as "psychobiotics" [90]. An animal study using mice showed that probiotic ingestion of Bifidobacterium longum and breve led to a reduction of depression and anxiety symptoms [200].…”

The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized by Gnotobiotic Mice

“…The 2009 Walkerton Health Study that assessed participants with irritable bowel syndrome (IBS) over an eight-year period found that depression and anxiety were important risk factors for the persistence of IBS symptoms [96]. Studies such as the Walkerton Study, which revealed associations between gut microbes and the brain provoked an imperative to determine if psychiatric symptoms can be driven by gut dysbiosis [97–100]. One study supported this notion by showing that germ-free mice exhibited reduced anxious behavior as compared to specific pathogen free mice [101].…”

Editorial focused issue ‘The role of nutrition in child and adolescent onset mental disorders’

“…On the other hand, the brain can also affect the gut bacteria, such that stress experienced by an organism, for example, can modify the gut microbiome, allowing colonization by pathogenic bacteria, which, in turn, can affect brain functioning [19]. As clearly described by Cenit et al in this issue [20], evidence from preliminary human studies suggests that dietary components that modulate gut microbiota may also influence ADHD development or symptoms, although further studies are warranted to confirm this hypothesis. Of interest is the fact that gut microbiota undergoes a dynamic non-random process of maturation until the age of 2-3 years when an adult-like microbiota structure is established.…”