The gut-microbiota-brain axis in autism: what Drosophila models can offer?

Abstract

The idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Inter-Species Rescue of Mutant Phenotype—The Standard for Genetic Analysis of Human Genetic Disorders in Drosophila melanogaster Model

“…Within Category 1 of high confidence for implication in ASD, there are currently 207 genes, which are also present in other similar gene lists or were previously identified in an extensive exome sequencing study [ 54 ]. Out of these, 203 have orthologs in D. melanogaster , with 141 genes having a Drosophila RNAi Screening Center integrative ortholog prediction tool (DIOPT) score of at least of 0.6 [ 55 ]. DIOPT scores are provided by the DIOPT integrative tool [ 56 ], which is currently at version 8.5 and enables the search of orthologs in different species among the data provided by 18 large-scale ortholog prediction tools.…”

“…DIOPT scores are provided by the DIOPT integrative tool [ 56 ], which is currently at version 8.5 and enables the search of orthologs in different species among the data provided by 18 large-scale ortholog prediction tools. The aforementioned list of orthologs with conclusive DIOPT scores includes the D. melanogaster genes Fmr1 , Pten or ubiquitin protein ligase E3A ( Ube3a ), with DIOPT scores of 0.73, 0.87 and 0.93, respectively [ 55 ].…”

Revealing the beneficial effects of a dairy infant formula on the gut microbiota of early childhood children with autistic spectrum disorder using static and SHIME® fermentation models

“…10 GBA works through bidirectional communication between the gut microbiota and the brain via multiple routes and mechanisms, including neural, endocrine, and immune pathways. 10,11 Both GM composition and metabolism influence the central nervous system (CNS) through the GBA, contributing to modulate brain activity, immune response, emotional state and many other homeostatic functions. 5,12 Still, the CNS is able to influence the composition of the GM and break the balance in intestinal permeability, modulating motility and secretion through activation of the hypothalamicpituitary-adrenal (HPA) axis, as well as of the autonomic and neuroendocrine systems with an immediate and direct impact on the GM.…”

The ortholog of human ssDNA-binding protein SSBP3 influences neurodevelopment and autism-like behaviors in Drosophila melanogaster

“…Genetic tractability and rich behavioral repertoire make Drosophila an excellent model for delineating genetic mechanisms of genes associated with psychiatric and cognition disorders, including ASD [17][18][19][20][21][22][23][24]. To determine the role of CNVs of SSBP3 in neurodevelopment and autism-associated behaviors, we used Ssdp overexpression and pan-neuronal knockdown strategy in male Drosophila fruit flies.…”