259C Poster - 02. Immunity and the microbiome
Saturday April 09, 1:30 PM - 3:30 PM

Kismet affects gut biomechanics, the gut microbiome, and gut-brain axis in Drosophila melanogaster


Authors:
Chloe Welch 1; Angelo Niosi 1; Henry Vo 1; Punithavathi Sundar 2; Aliyah Penn 1; Jeffrey Cavanaugh 1; Prince Yadav 1; Wendy Lee, PhD 2; Mikkel Herholdt Jensen, PhD 1; Eliza J. Morris, PhD 1; Kimberly Mulligan, PhD 1

Affiliations:
1) California State University, Sacramento; 2) San Jose State University

Keywords:
m. microbiome; c. models of ASD

The gut microbiome may contribute to the pathophysiology of neurodevelopmental disorders (NDDs), yet it is unclear how NDD risk genes affect gut physiology in a manner that may alter bacterial colonization. We addressed this question using Drosophila melanogaster with a mutation in kismet (kis), the ortholog of the human autism risk gene Chromodomain Helicase DNA Binding Protein 8 (CHD8). We used kis mutant flies to examine gut biomechanics, gut microbiota, and to explore the connection between gut microbiota and behavior. To quantify changes in gut tissue mechanics, we affixed whole guts between two clips mounted on a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision. Our measurements revealed significant changes in the mechanics of kis mutant guts compared to wild-type, in terms of elasticity, strain stiffening, and ultimate tensile strength. To characterize the gut microbiomes, we used 16S metagenomic sequencing and found that loss of kis profoundly impacted the abundance of many bacterial taxa in the midgut. To investigate the putative connection between the gut microbiome and behavior, we treated kis mutant and control flies with an antibiotic and then evaluated courtship behavior. Depletion of the gut microbiome rescued courtship defects of kis mutant flies, indicating a connection between the mutant gut microbiome and behavior. In striking contrast, depletion of the gut microbiome in the control strain induced courtship defects. This result demonstrates that antibiotic treatment can have either positive or negative impacts on behavior, depending on the status of gut dysbiosis prior to treatment.