Leaky guts and the maternal immune activated mouse model of autism

CC BY-SA by Wolfgang Lonien

CC BY-SA by Wolfgang Lonien

Continuing a theme of the gastrointestinal (GI) tract potentially being an important organ when it comes to at least some cases of autism, the paper by Elaine Hsiao and colleagues* adds an interesting additional layer to the science with a specific focus on the permeability of the GI barrier and the concept of maternal immune activation in a mouse model of autism.

Think of the human GI tract as the engine which powers the body, converting the food and drink we consume into essential nutrients which fuel growth and power a multitude of important biological reactions vital to good health and wellbeing. Containing several important chemicals including the enzymes and trillions of bacteria which inhabit our deepest, darkest recesses which help decompose our foods, the GI tract also acts as an important barrier. This barrier is finely poised to allow nutrients from within the GI tract to enter general circulation of the body but at the same time contain foreign matter such as undigested food or even gut bacteria from meeting other parts of the body and particularly, our immune system, and subsequently provoking a response.

The work from Hsiao and colleagues builds upon several previous studies hinting that there may be issues with the GI barrier associated with cases of autism. More commonly known as gut hyperpermeability or ‘leaky gut’, there has been much speculation down the years as to what relationship abnormal GI permeability might have to autism; also intermixed with discussion about potential dietary effects.

In their latest paper Hsiao and colleagues describe their results looking at offspring mice born to mothers who were artificially induced to present with activation of the immune system similar to the process of how the body reacts when it meets infection or other pathogenic insult. This model known as the maternal immune activation (MIA) hypothesis has previously described how offspring mice and monkeys born to MIA mothers show behaviours which could be interpreted as overlapping with some of those observed in autism and other conditions. The authors report that alongside the presence of such behaviours, MIA related offspring also show particular physiological issues with the GI tract in the form of abnormal GI permeability, and that such permeability issues were positively modified by the introduction of a specific type of bacteria found in the GI tract.

Caution needs to be applied however before extrapolating these findings from a mouse model to humans; the work also requiring independent replication. That being said, the research opens up several potentially important possibilities insofar as providing both a model for a particular type of autism and how it might come about, as well as bridging a gap between immune function and GI physiology associated with cases of autism.

 

* Hsiao EY. et al. Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell. 2013. 5 December.

Further commentary on this study can be found at: http://questioning-answers.blogspot.co.uk/2013/12/leaky-mice-guts-bacteria-autism-part-2.html