An autism spectrum disorder-related risk gene impacts gut tissue mechanics and the gut microbiome in Drosophila melanogaster*

The bacteria in the human gastrointestinal (GI) tract, the so-called gut microbiome, have co-evolved with the host to form a symbiotic relationship and is an essential component of human health and healthy development. A growing body of research has revealed an intricate reciprocal relationship between neuronal development and the gut microbiota, in which changes in neuronal development affects the gut microbiota and vice versa. However, the role of the biophysical properties of the gut in this so-called gut-brain axis is poorly understood. Here, we employ a Drosophila melanogaster fly model carrying a mutation in the autism spectrum disorder-related risk gene chromatin helicase DNA-binding 8/kismet (CHD8/kis, or “kis” for short). We found that kis mutant flies exhibit changes in their gut mechanics, gut microbiome and organism behavior compared to wild-type flies. Interestingly, our mechanics measurements revealed changes in the mechanics of the kis mutant fly gut, both in terms of the strain stiffening behavior and overall elasticity. Our results support the idea that gut tissue mechanics may play a role in the gut-brain axis paradigm, and future work will further explore any reciprocal relationship between gut mechanics, the microbiome, and neuronal development.