**1. Introduction**

The microbiota-gut-brain axis is a bidirectional communication pathway between the microbiota, gut and central nervous system (CNS). It has been estimated that over 10<sup>14</sup> microorganisms, which include bacteria, archaea, and eukaryota, reside in the gastrointestinal tract (GI-tract) [1]. According to the latest study, this results in an approximately equal number of microbial compared to human cells in an individual [2]. The microorganisms residing in the GI-tract play an important role in protecting humans from potential GI pathogens [3], and also exert neuroactive properties which explains why this ecosystem does not only influence the gut, but also the brain. Research shows the great importance of a healthy microbial composition in the gut at an early stage in life (2–3 years of age), a period also characterized by intense neurodevelopment in humans. Several reports conclude that early gut dysbiosis can influence the neurodevelopment in the short run and may also lead to mental health issues later in life [4,5].

Research highlights this risk, as gut dysbiosis in child or adulthood has not only been associated with various diseases, such as irritable bowel syndrome [6] or obesity [7], but also with psychiatric disorders as, for example, depression [8], Parkinson s disease (PD) [9], schizophrenia [10], autism spectrum disorder (AS) [11], and lastly, attention-deficite-hyperactive-disorder (ADHD) [12].

ADHD is an early onset neurodevelopmental disease that, according to the fifth edition of Diagnostic and Statistical Manual (DSM-V), can be characterized into different representations: Hyperactivity and/or impulsivity, inattentiveness or all combined [13]. The worldwide prevalence of ADHD in children under the age of 18 ranges from 5.3% [14] to 7.2% [15], making it the most frequent neurobehavioral diagnosis in children. Interestingly, varying prevalence levels are reported in different geographies, which are primarily due to different characteristics of methods employed for ADHD diagnosis rather than geographic variations [14]. Nonetheless, 30–60% of the children continue to show symptoms into adulthood and thus, 1–6% of the population develop adult ADHD [16]. This is predominantly represented by the inattentive type [17].

This literature review attempts to identify and discuss factors that may influence the microbiome, and thus, could be associated with the development or progression of ADHD. Thereby we concentrate solely on the influence of bacteria rather than archaea and eukaryota. Furthermore, we evaluate the biochemical changes in ADHD patients and to what extent these can be related to microbial alterations in the gut. Finally, we reconfirm known biomarkers and deduce possible new ones for the diagnosis of ADHD and conclude what factors worsen or alleviate the development and progression of ADHD as this might lead to potential intervention methods of the neurodevelopmental disorder.
