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“Recent research suggests that the brain-gut-microbiome … may play a role in the pathophysiology of ADHD and other neuropsychiatric disorders.”

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by symptoms of inattention, hyperactivity, and impulsivity. Approximately six million children between the ages of three and seventeen are diagnosed with ADHD, and the disorder has shown an increase in prevalence from 6.1% to 10.2% in the 20-year period from 1997 to 2016. It is unclear if this increase is a result of altered diagnostic criteria or represents a true increase of the disorder. Recent research suggests that the brain-gut-microbiome system, the bidirectional communication system between the gastrointestinal tract and the central nervous system, may play a role in the pathophysiology of ADHD and other neuropsychiatric disorders. Based on evidence from mostly preclinical studies, the gut microbiome, including bacteria, fungi, viruses, and archaea, can influence this communication pathway, potentially affecting brain function and behavior.

A study published in the Journal of Child Psychology and Psychiatry in 2023 by Liang-Jen Wang et al. from the Department of Child and Adolescent Psychiatry Chang Gung University College of Medicine in Taiwan focuses on the fungal component of the gut microbiome, known as the mycobiome. The research team hypothesized that dysbiosis in the gut mycobiome, specifically an imbalance in the prevalence of fungal species, is linked to ADHD. In order to test this hypothesis, they investigated the composition of the gut mycobiome in children with ADHD compared to healthy controls and to examine the impact of this dysbiosis on intestinal permeability, a condition often referred to in the lay press as ‘leaky gut.’

The study involved 70 children, split evenly between ADHD patients and healthy controls. DNA was extracted from these samples, and a DNA sequence which allows the identification of fungal species was sequenced using next-generation sequencing. This method allows for a detailed analysis of the composition of the fungal community in the gut.

“Specifically, those with ADHD exhibited increased levels of Ascomycota fungi and a notable reduction in Basidiomycota fungi in their gut mycobiome, in contrast to the control group.”

Significant differences were found in the fungal community composition between the ADHD and control groups. Specifically, those with ADHD exhibited increased levels of Ascomycota fungi and a notable reduction in Basidiomycota fungi in their gut mycobiome, in contrast to the control group. Additionally, there was an increased relative abundance of Candida albicans in the gut of children with ADHD. Based on their findings, the authors suggested a potential link between specific fungal species and ADHD.

To explore the biological effects of the identified fungal dysbiosis, the researchers conducted in vitro testing using cultured Caco-2 cells, a test used to mimic the permeability of the intestinal barrier. The study observed that secretions from Candida albicans increased the permeability of these cultured cell layers, suggesting that the presence of this fungus in the gut might contribute to the increased intestinal permeability seen in ADHD patients. A more permeable intestinal barrier has been implicated in activating the gut-based immune system resulting in widespread low grade inflammation and alterations in brain function.

While Candida yeasts are typically harmless and common in the human gut, their excessive growth may impact health, sometimes influenced by certain medications and possibly by dietary factors, such as high sugar consumption. This overgrowth can impact gut permeability, leading to low-grade inflammation. A compromised intestinal barrier allows gut microbes and harmful substances to enter the bloodstream, increasing the risk of widespread low-grade inflammation throughout the body, including the brain. The brain-gut microbiome system plays a crucial role in these interactions.

In another attempt to explore a possible relationship between dysregulation in the brain-gut-microbiome connection in ADHD, a study by Esther Aarts and her team at Radboud University, published in PLoS ONE in 2017, looked at the possible role of certain gut bacteria and their neuroactive metabolites. This research focusing on gut bacteria uncovers a significant increase in Bifidobacterium in ADHD patients, correlating with an enhanced ability of the gut bacteria to produce the building blocks for dopamine, a crucial brain chemical that influences reward and pleasure. This microbiome alteration is linked to weaker brain reactions to rewarding stimuli, which is a characteristic of ADHD, as observed in brain imaging scans. The authors emphasize the need for more research to confirm these findings and explore their implications for understanding and treating ADHD.

“The cross-sectional nature of the research restricts its ability to establish causal relationships.”

While both studies shed light on possible new aspects of ADHD’s development, it’s important to remember that the correlational findings are only a preliminary step in understanding the role of microbial organisms in the gut with the symptom complex of ADHD. The study by Wang and coworkers may have identified certain aspects of the gut mycobiome dysbiosis and its potential association with ADHD, but as is the case with most human brain disorders, it didn’t provide evidence for a causal role of the observed dysbiosis in clinical ADHD symptoms. For example, the increased anxiety present in many ADHD patients may be the primary reason for the observed microbiome alterations, and the study provides no evidence that an altered mycobiome can actually cause ADHD symptoms.

“Dr. Mayer recommends … a diverse, plant-based diet, foods rich in prebiotics and probiotics, reducing sugar, and focusing on stress management, sleep, and moderate exercise.”

Dr. Emeran Mayer, author of The Mind-Gut Immune Connection and the gut-friendly recipe book Interconnected Plates, recommends various general strategies for a healthier gut, such as a diverse, plant-based diet, foods rich in prebiotics and probiotics, reducing or eliminating sugar, and focusing on stress management, sleep hygiene, and regular moderate exercise. It remains to be determined if such a general holistic approach has any therapeutic benefit for ADHD symptoms.

In conclusion, the studies by Wang et al. and Aarts et al adds to the limited research exploring alterations in the gut-brain-microbiome system in ADHD. Focusing on the mycobiome emphasizes the potential influence of fungal species in the gut on brain health and behavior a largely unexplored area of research. In view of the sparsity of human gut mycobiome studies in neurodevelopmental disorders like ADHD and Autism Spectrum Disorder, such studies are highly important.