NDD and the Gut Microbiome
We are exploring the links between the gut microbiome, fatigue, and behaviours of concern in children and youth with NDDs.
Children and youth diagnosed with an NDD have high rates of co-occurring behaviors of concern and chronic fatigue. While fatigue is defined as an internal and subjective feeling of tiredness, many individuals with NDDs are unable to communicate their internal states. As such, documentation of chronic sleep problems and sleep deprivation are often used as an observable indicator of chronic fatigue in the NDD population. Findings linking sleep problems to behaviours of concern among children and youth with NDDs are consistent and sleep problem severity is associated with higher scores of behavioral severity.
The etiology of behaviours of concern and fatigue in NDDs is largely unknown. But converging evidence in animal models and humans suggests a role for gut dysbiosis. The gut microbiome is a key regulator of intestinal physiology, neuroimmune crosstalk, and host behavior. Intriguingly, up to 70% of individuals with NDDs have impaired gastrointestinal function and evidence suggests that these problems potentiate behaviours of concern. Moreover, individuals with NDDs show a higher prevalence of gut dysbiosis when compared with controls in terms of microbiome diversity, bacterial composition, and metabolome dysfunction. Like individuals with NDDs, several animal models of environmental or genetic risk factors for NDDs display altered microbiota signatures. Remarkably, restoring a more typical microbiome in these animal models ameliorates some behaviours. In a proof of concept study, some individuals with ASD showed significantly reduced abnormal behaviours in response to antibiotics targeting Clostridium overgrowth.
In addition, antibiotics D-cycloserine and minocycline have been shown to treat behavioural symptoms in Autistic individuals and animal models of NDDs. While these results implicate the gut microbiome as a therapeutic target, there is little consensus on which bacterial species play a causal role in specific NDD manifestations and co-occurring conditions. As such, further studies are needed to investigate whether particular microbiome and/or volatile metabolic signatures are associated with specific NDD-associated dietary regimens, clinical features, and co-occurring conditions like behaviours of concern and fatigue.
As a first step in this biomarker discovery, we are validating our approach and methods in a pilot study of children and youth with NDDs and co-occurring behaviours of concern and fatigue. We will combine clinical information with breath and stool samples at three time points from subjects with NDDs and sibling matched controls. These data may identify NDD-specific biomarker profiles associated with behaviours of concern and fatigue and inform future hypothesis-driven studies for therapeutic testing.
Collaborators:
Dr. Kendall Corbin PhD, Assistant Professor, Department of Horticulture, University of Kentucky
Dr. Heather Bean PhD, Associate Professor, School of Life Science, Arizona State University