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The bacterial community (or microbiota) that resides in the human gastrointestinal tract is known to have many effects on human physiology. It has been implicated in Autism Spectrum Disorder (ASD), since several changes in the gut microbiota of ASD individuals have been reported in the literature. However, methods to investigate the possible effects of the gut microbiota on the developing nervous system have not been forthcoming. The overall objective of this thesis project was to determine the value of zebrafish as a method of interrogating the effects of the gut microbiota from ASD individuals on behaviour and neural development. Towards this goal we first attempted to colonize the gastrointestinal tracts of 5 day old, germ-free zebrafish with bacterial strains originally isolated from human sources, and we successfully established 2 species – Lactobacillus paracasei and Eubacterium limosum. In a parallel study, we surveyed the gut microbiota of migrant Somali families (a community that exhibits a high incidence of ASD) and found that bacteria of the genus Pseudomonas were significantly more prevalent in the ASD gut microbiota. We also assessed metabolic products of the human gut microbiota for their effects on zebrafish, with a particular focus on short-chain fatty acids, which are a group of metabolites whose abundance is altered in individuals with ASD. We found that one such metabolite, propionate, had dramatic effects on both behaviour and neural gene expression in week-old developing zebrafish. From these experiments we determined that the flexibility and sensitivity of the zebrafish model is well suited for a wide range of microbiological, metabolomic, and genetic studies. In conclusion, the use of zebrafish for microbial ecology research (particularly in the context of neurobehavioural disorders such as ASD) is supported. Ontario Graduate Scholarship |
