The intricate interplay between the gut microbiota and the brain, known as the gut-brain axis, plays a pivotal role in neurodevelopment, function, and behaviour. Recent research underscores the profound influence of gut dysbiosis on various neurodevelopmental conditions, notably autism spectrum disorder (ASD). Moreover, a significant subset of individuals with ASD experience gastrointestinal (GI) disturbances, suggesting a potential link between gut dysfunction and ASD pathophysiology.
In our study, we leverage the well-established neuroligin-3 knockin (NL3R451C) mouse model of autism to investigate the connection between altered gut function and microbial dysbiosis. Notably, NL3R451C mice harbor the same X-linked missense mutation found in ASD patients with comorbid GI dysfunction, providing a unique opportunity to dissect the underlying mechanisms.
Expanding beyond conventional faecal sampling, our study employs a comprehensive approach, encompassing sampling along the gastrointestinal tract. Our analysis unveils notable shifts in bacterial composition and diversity patterns across the small intestine of NL3R451C mice compared to their wild-type counterparts, reinforcing previous observations of altered gut transit and neurobiology in this model. Particularly striking is the apparent loss of differentiation between functional regions of the gut in NL3R451C mice.
These results shed new light on the gut-brain connection in autism, offering valuable insights into the interplay between gut function, microbial communities, and ASD pathogenesis. Moreover, our findings hold promise for guiding the development of targeted therapeutic interventions to alleviate gut dysfunction in individuals with ASD, thus contributing to enhancing their quality of life.