Drosophila as a Model for Microbiota Studies of Neurodegeneration

Abstract

Accumulating evidence show that the gut microbiota is deeply involved not only in host nutrient metabolism but also in immune function, endocrine regulation, and chronic disease. In neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis, the gut-brain axis, the bidirectional interaction between the brain and the gut, provides new route of pathological spread and potential therapeutic targets. Although studies of gut microbiota have been conducted mainly in mice, mammalian gut microbiota is highly diverse, complex, and sensitive to environmental changes. Drosophila melanogaster, a fruit fly, has many advantages as a laboratory animal: short life cycle, numerous and genetically homogenous offspring, less ethical concerns, availability of many genetic models, and low maintenance costs. Drosophila has a simpler gut microbiota than mammals and can be made to remain sterile or to have standardized gut microbiota by simple established methods. Research on the microbiota of Drosophila has revealed new molecules that regulate the brain-gut axis, and it has been shown that dysbiosis of the fly microbiota worsens lifespan, motor function, and neurodegeneration in AD and PD models. The results shown in fly studies represents a fundamental part of the immune and proteomic process involving gut-microbiota interactions that are highly conserved. Even though the fly’s gut microbiota are not simple mimics of humans, flies are a valuable system to learn the molecular mechanisms of how the gut microbiota affect host health and behavior.

Insect Models in Nutrition Research

“…Impressively, the characterization of microbes and regenerative stem cells in the Drosophila gut has led to the use of Drosophila as a model to study the regulation of the gut epithelium and its microbiome [ 154 ]. Although Drosophila gut microbes do not mimic the human gut microbiome directly, they are sufficient to investigate how the microbiome affects health and behavior [ 155 , 156 ], facilitated by the genetic tools and resources available in Drosophila [ 153 ]. For example, Drosophila hosts only a small number of bacterial populations in its gut, including species also present in the human microbiome [ 157 ].…”

“…Neurodegenerative disorders including AD and PD are the main causes of dementia in the elderly human population [ 162 , 163 , 164 , 165 ]. The gut microbiome is involved not only in nutrient metabolism but also in the onset and progression of neurodegenerative diseases [ 155 , 166 ]. Dysbiosis in the Drosophila gut reduces the lifespan, inhibits motor function, and causes neurodegeneration in AD and PD models [ 155 ].…”

“…The gut microbiome is involved not only in nutrient metabolism but also in the onset and progression of neurodegenerative diseases [ 155 , 166 ]. Dysbiosis in the Drosophila gut reduces the lifespan, inhibits motor function, and causes neurodegeneration in AD and PD models [ 155 ]. The potential of Lactobacillus probiotics to reverse the progression of AD has been demonstrated in a Drosophila AD model [ 166 ].…”

Drosophila Model for Studying Gut Microbiota in Behaviors and Neurodegenerative Diseases

“…However, the versatile organism, Drosophila, is a powerful research model that allows scientists to investigate the mechanisms by which gut microbes affect the brain functions (Figure 1a,b). The microbes can be genetically tagged with a fluorescent protein, thus, their distribution in the digestive tract of Drosophila can be visualized (Figure 1c) [21,22].…”

Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease

“…Recently, Drosophila has been proved as an excellent model organism for dissecting the mechanism and drug library screening, such as cancer, aging, nociception, neurodegenerative diseases. Until now, Drosophila as a model helps researchers get the Nobel Prize in Physiology or Medicine for six times ( Kitani-Morii et al, 2021 ). The advantages of fly are small size, genetic amenability, low-cost maintenance, and excellent genetic and molecular tools.…”