Gut-brain communication consists of bidirectional routes between cognitive centers of the brain and peripheral intestines. This bidirectional communication is the result of the interplay between enteroendocrine cells (EECs), enteric nervous system, central nervous system, the vagus nerve, and our microbiota. Multiple studies have associated gut microbial dysbiosis with neurological disorders or altered behavioral phenotype. Specifically, recent work in Autism Spectrum Disorder associates Clostridium species in the etiology of the disorder, as well as other neuro-developmental disorders. In order to define the potential role of the Clostridium bacteria in the etiology of ASD, we focused on Clostridium celatum, a bacteria found to be enriched in children with ASD and part of normal human gut flora and is non-pathogenic. We studied the impact of C. celatum on the core symptoms of autism in a rodent model by feeding C.celatum to C57BL/6 mice and Maternal Immune Activation (MIA) mice model of autism, and by performing various behavioral tests related to anxiety and sociability, we observed that we were able to modulate behavioral phenotypes in mice using C. celatum.
The microbiota is thought to interact with the brain through a number of pathways including the immune system, microbial metabolites, enteroendocrine cells (EECs), and the vagus nerve. The focus of the second part of the project was to determine if C. celatum and the other taxa in the gut microbiota can directly interact with these gut sensory cells and eventually transduce the signals to the brain via the vagus nerve. To do so, we successfully isolated and cultured EECs from the small intestine of CCK-GFP transgenic mice and crosslinked them with all the gut microbiota using a cell impermeable cross-linking reagent. 16S rRNA sequencing analysis of samples with C. celatum indicated that C. celatum doesn’t cross-link with EECs. However, analysis of the samples containing all the gut microbiota crosslinked with EECs suggested a significantly higher abundance of the taxa belonging to the Rhizobiaceae and Lactobacillaceae families that cross-linked with EECs.