New Link Between Autism and the Gut Microbiota




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The fact that diet has a huge influence on our health should be common knowledge by now. But what research has been showing us in recent years is just how fundamental the influence of diet on our health can be. Surprising links between diet and a number of previously unsuspected diseases are being continuously established. But food does not affect us only after we are born, it actually starts to shape our health during pre-natal development.

Poor nutrition during pregnancy is known to be associated with developmental disorders. Maternal obesity due to high-fat diets during pregnancy, for example, has been linked to a number of conditions, including the development of autism spectrum disorder (ASD) in the offspring. Since obesity is on the rise across all contexts, obesity during pregnancy is more and more a matter of concern.

Many of these associations between diet and disease, including neurological diseases, are now known to be modulated by the gut microbiota. Research on the gut-brain axis is a blooming field where new and important findings keep streaming. And just as our gut can have such a huge impact on our health when we are fully developed, it seems likely that it can also shape it when we are still developing, including in the womb.

Looking into the impact of maternal diet on the gut microbiota and determining its consequences therefore seems like a highly relevant research topic. Indeed, maternal obesity has been associated with alterations in the gut microbiota of the offspring in humans. It is possible that neurodevelopmental disorders that have been associated with maternal obesity may also occur through the action of the gut-brain axis.

Individuals with ASD often also have gastrointestinal problems and dysbiosis of the gut microbiota, being unclear whether an altered gut flora is a cause of a co-morbidity of ASD. It has been suggested that changes in the gut microbiota may indeed play a role in the development of the behavioral symptoms associated with ASD, but the possible mechanisms of this link remain unknown.

The journal Cell recently published a noteworthy study regarding the impact of maternal diet on ASD, establishing a new role for the gut microbiota. Research carried out in mice showed that a maternal high-fat diet leads to changes in the gut microbiota of the offspring, inducing a reduction in specific bacterial species. These changes were associated with behavioral alterations, namely social deficits that mimic those of autism spectrum disorder.

The correction of their gut microbial profile was able to reverse the social deficits induced by the maternal high-fat diet. It was also shown that germ-free mice presented social impairments that could be reversed by transplanting fecal microbiota from the offspring of mice with a regular diet, while transplants from the offspring of mice on a high-fat diet was unable to induce the same effect. One particular bacterial species, named Lactobacillus reuteri, was shown to be dramatically reduced in the maternal high-fat diet offspring. The administration of L. reuteri to those mice was also able to restore their social behavior.

Data from this study also indicates a possible route through which L. reuteri improves social behavior – it increased the levels of oxytocin in the paraventricular nuclei of the hypothalamus, where it is primarily synthesized. Direct treatment of the high-fat diet offspring with oxytocin also normalized their social behavior.

Therefore, this indicates that the high-fat diet of the mother may lead to a decrease in the levels of L. reuteri in the gut of the offspring, which in turn leads to a decrease in the production of oxytocin and of its action on the fetus. The precise mechanism by which L. reuteri modulates the production of oxytocin in the brain remains to be determined. The authors of this study hypothesize that this may happen though the vagus nerve, one of the main communication routes between the brain and the gut, as supported by other studies.

There have already been a number of studies linking the gut microbiota to the development of ASD. For example, the restoration of gut permeability using probiotics in a mouse model of ASD was able to improve some behavioral dysfunctions, but not social behaviors. In this study, on the other hand, social behavior was improved, but other behavioral patterns associated with ASD were not. This points towards the possibility that a selective combination of probiotics may be a useful therapy for ASD.

Importantly, this adds to the growing notion of just how important our gut and our diet are.

References

Bresnahan, M., Hornig, M., Schultz, A. F., Gunnes, N., Hirtz, D., Lie, K. K., … Lipkin, W. I. (2015). Association of maternal report of infant and toddler gastrointestinal symptoms with autism. JAMA Psychiatry, 72(5), 466. doi:10.1001/jamapsychiatry.2014.3034

Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. (2016). Microbial Reconstitution reverses maternal diet-induced social and Synaptic deficits in offspring. Cell, 165(7), 1762–1775. doi:10.1016/j.cell.2016.06.001

Connolly, N., Anixt, J., Manning, P., Ping-I Lin, D., Marsolo, K. A., & Bowers, K. (2016). Maternal metabolic risk factors for autism spectrum disorder-an analysis of electronic medical records and linked birth data. Autism Research. doi:10.1002/aur.1586

Galley, J. D., Bailey, M., Kamp Dush, C., Schoppe-Sullivan, S., & Christian, L. M. (2014). Maternal obesity is associated with alterations in the gut Microbiome in toddlers. PLoS ONE, 9(11), e113026. doi:10.1371/journal.pone.0113026

Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., … Mazmanian, S. K. (2013). Microbiota modulate behavioral and physiological abnormalities associated with Neurodevelopmental disorders. Cell, 155(7), 1451–1463. doi:10.1016/j.cell.2013.11.024

Krakowiak, P., Walker, C. K., Bremer, A. A., Baker, A. S., Ozonoff, S., Hansen, R. L., & Hertz-Picciotto, I. (2012). Maternal metabolic conditions and risk for autism and other Neurodevelopmental disorders. PEDIATRICS, 129(5), e1121–e1128. doi:10.1542/peds.2011-2583

Mayer, E. A., Padua, D., & Tillisch, K. (2014). Altered brain-gut axis in autism: Comorbidity or causative mechanisms? BioEssays, 36(10), 933–939. doi:10.1002/bies.201400075

Image via tasha / Pixabay.

Sara Adaes, PhD

Sara Adaes, PhD, has been a researcher in neuroscience for over a decade. She studied biochemistry and did her first research studies in neuropharmacology. She has since been investigating the neurobiological mechanisms of pain at the Faculty of Medicine of the University of Porto, in Portugal. Follow her on Twitter @saradaes
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