Attention-Deficit/Hyperactivity Disorder and the Gut Microbiota–Gut–Brain Axis: Closing Research Gaps through Female Inclusion in Study Design

Abstract

The gastrointestinal tract harbors a densely populated community of microbes that exhibits sexual dimorphism. Dysbiosis of this community has been associated with chronic human disease states ranging from metabolic diseases to neuropsychiatric disorders (NPDs). The gut microbiota–gut–brain axis (GMGBA) is a bi-directional pathway that facilitates the interaction of the gut microflora with host physiological functions. Recently, research surrounding the potential roles of the GMGBA in the development of NPDs (e.g., depression, anxiety, and autism spectrum disorders (ASDs)) has increased. However, the role of the GMGBA in attention-deficit/hyperactivity disorder (ADHD), an NPD that affects an estimated 8.4% of children (5.1% of female and 11.5% of male children) and 4% of adults (with a male–female odds ratio of 1.6) in the United States, remains understudied. Herein, we synthesize the current literature regarding the GMGBA, ADHD, and the potentially relevant intersections between the GMGBA and ADHD. Recommendations are presented for pathways of future research into the role(s) of the GMGBA in ADHD etiology and symptomatology. Particular focus is given to the potential for the variable of host sex to act as an outcome modifier of the relationship between the GMGBA and ADHD.