Drosophila larvae are small, white and glossy with a similar appearance to worms. Within days they increase around fold in weight.
Adults in the wild are tan with black stripes on the back of the abdomen and vivid red eyes. However, there are many visible genetic mutations , including many different eye colours, which are valuable for geneticists studying Drosophila. Females live for about one month at room temperature but this can increase to over two months at lower temperatures. A female may lay eggs per day throughout her lifetime at room temperature. Daily egg production is reduced at lower temperatures. The Drosophila feeds and breeds on fermenting fruit or on other sources of fermenting sugar such as waste in drains or rubbish bins.
Oxford Instruments. Investors Careers. Life Science Cameras. Control Software. Physical Science Cameras. OEM Portfolio. Support Service and Support. Learning Centre Asset. Becher, John E. Pool, and Marcus C. Franz, W. Wood, and P. Tomer, K. Khairy, F. In humans, the gastrointestinal tract is populated by a multiplicity of microorganisms including more than different bacterial species.
In the present context, the so-called microbiota refers to the commensal bacteria present in the colon [ 31 ]. In healthy human subjects, the microbiota shows a distinguished composition that consists of five phyla: mainly Bacteroidetes Bacteroides ssp.
This microbiota composition is vulnerable during childhood and advanced age and rather stable during adulthood [ 33 ]. Various studies have reported a high microbiota diversity between subjects suggesting an association with different diets and obesity and consequently in energy homeostasis [ 32 ]. Taking advantage of the sophisticated genetic tools available in the fruit fly Drosophila melanogaster , its complex gastrointestinal system and the presence of a clear microbiota, it would be a predestined model to unravel host-microbiota interactions related to nutrition.
The gut of Drosophila melanogaster hosts a limited number of commensal gut bacteria ranging from 3 to 30 species, including Lactobacillus plantarum as the most prevalent, Acetobacter pomorum , A. Interestingly, populations of Lactobacillus species are common to both fly midguts and animal small intestines [ 36 ] and have been associated with several biological functions in Drosophila melanogaster , including larval growth, food uptake, and protection from malnutrition or oxidative stress, similar to health-promoting properties of Lactobacillus in mammals [ 37 ].
Similarly, Pais et al. Interestingly, in wild-caught fruit flies, 35 different OTUs, corresponding to Enterobacteriaceae, Acetobacteriaceae mainly Acetobacter and Gluconobacter species , Leuconostocaceae , and Bacillaceae, were identified as the most prevalent families, partly containing bacterial strains that are able to stably colonize the fly gut, such as L.
Sterile or axenic fly strains reared under germfree conditions may be generated either by applying low doses of streptomycin to the diet or by performing egg dechorionation [ 43 ]. To obtain flies with a defined microbial community gnotobiotic flies , flies will either be exposed to correspondingly inoculated sterile diets or embryos will encounter microbial species of interest [ 44 ].
In an experiment using axenic and gnotobiotic flies, Dobson et al. A recent publication demonstrated that the elimination of the microbiota altered the expression of immune response-associated genes, as well as genes connected with oxidative stress and general detoxification, in the head of young adult Drosophila melanogaster [ 46 ].
As mentioned earlier, nutrigenomics refers not only to gene-nutrient interactions but also to nutrient-epigenetic, nutrient-proteomic, nutrient-metabolomic, and nutrient-microbiome interactions Fig. Overview of the nutrigenomics approach in the model organism Drosophila melanogaster. An organism ingests complex foods which are degraded into nutrients that interact with the microbiome. The fruit fly can be used as a model organism in nutrigenomics, as changes in the microbiome, transcriptome, epigenome, proteome, and metabolome due to an interaction with the nutritional environment are detectable and evaluable by several methods pictograms used are from vecteezy.
Diverse transcriptomic tools may be used in nutrigenomics research in Drosophila melanogaster including microarrays, to deliver information on changes in the mRNA expression following the dietary intake of a specific nutrient [ 7 ], and RNA sequencing [ 10 ] and next-generation sequencing NGS technologies [ 47 ], to analyze regions of interest in the genome, providing promising results and solutions to nutrigenomics studies by identifying new mutations in inbred fly strains. In addition, studies of QTL [ 48 ], representing a genome region that causes a significant variation in a quantitative trait, may be used in identifying signaling pathways involved in the metabolism of specific nutrients.
Until then, large-scale RNAi screens of gene function have been mainly performed in Caenorhabditis elegans , although it exhibits systemic RNAi for which reason the gene interference cannot be referred to a specific cell type [ 49 ].
This makes it easier to study the overexpression or the misexpression of fly homologous genes and proteins, helping to establish fly models to study human diseases. The genome refers to the genetic material of an organism consisting of DNA. This indicates that the chromosomes need to be condensed several thousand times to fit perfectly into the small nucleus which is mediated by chromatin folding.
During the last decades, it has become obvious that this DNA organization essentially contributes to the regulation of the gene expression which is referred to as epigenetic regulation [ 52 ]. The transcriptome refers to all messenger RNAs present in one cell or a population of cells at a defined time [ 53 ].
The analysis of the transcriptome has been mainly dominated by microarray analysis provided by different companies, including Affymetrix, Agilent Technologies, and Illumina. It is stated that this methodology offers—compared to microarrays—the advantage of the detection of lower abundant and wider ranges of transcripts [ 54 ]. By comparing the intake of two different obesogenic diets, RNAseq analysis from Drosophila heads revealed significant differences in the transcriptome.
While genes associated with immunity, metabolism, and hemocyanin have been mainly affected in flies fed with a high-fat diet, genes connected with cell cycle checkpoint kinases CHK , cell cycle activity, and DNA binding and transcription have been upregulated in flies receiving a high-sugar diet [ 10 ]. In a recent study by Azuma and colleagues [ 55 ], plant bioactives have been applied to detect antiobesogenic effects in a fly model of obesity.
RNAseq analysis has been performed to detect differentially regulated genes in male and female flies fed with a coconut-oil-supplemented high-fat diet, either in the presence or in the absence of quercetin glycosides QG or epigallocatechin gallate EGCG. This is—as far as we know—one of the first publications presenting lists of differentially regulated genes in obese flies using RNAseq data analysis. These results have been supported by functional analysis showing lower triglyceride levels in flies under QG or EGCG supplementation.
Gene set enrichment analysis has shown a downregulation of TOR, metabolism, Wnt, p53, and immune processes, whereas genes associated with the cell cycle have been increased following dietary LCA treatment [ 56 ].
An earlier study by Ye and colleagues [ 7 ] performed transcriptomic analysis by using the microarray technology. Preliminary results have been generated in flies being exposed to different energy sources in their diets, including sucrose as a control, palmitic acid, soy, and beef. Changes in the gene expression levels of ca.
Additionally, in Drosophila larvae, a starvation of amino acids changed the transcriptome, especially metabolism-associated genes, mainly involved in the TOR pathway [ 57 ]. The term epigenetics defines heritable phenotype alterations which are not mediated by a change in the DNA sequence. The epigenome changes within the cells and is more dynamic compared to the genome [ 59 ].
It has been documented that our diet is able to induce epigenetic alterations that, in consequence, affect biomarkers of metabolic modulations in different model organisms as well as in human subjects. A very famous example of epigenetic effects due to dietary changes are humans that survived the so-called Dutch hunger winter in [ 60 ]. Several years later, researchers were able to detect changes in different metabolic markers in their offspring, such as the glucose tolerance [ 61 ], which resulted from a change in the methylation pattern of specific genes due to a limited availability of calories during the gestational period [ 62 , 63 ].
To detect epigenetic changes in a biological sample, MethyLight technology, pyrosequencing, chromatin immunoprecipitation-on-chip ChIP-on-chip , and quantitative methylation-specific polymerase chain reaction QMSP followed by pyrosequencing can be applied [ 59 ]. All methods use the sodium bisulfite treatment as the compound reacts with unmethylated cytosine and converts it into uracil, which helps to deliver information on DNA methylation via PCR technology [ 59 ].
The detection of changes in microRNA expression is mainly performed by gene-chip microarray technology Affymetrix , while histone modifications are detected by applying specific monoclonal antibodies against histone modifications or by a ChIP-seq assay followed by NGS [ 59 ].
Studying diet-related effects on epigenetic mechanisms in fruit flies has just recently started [ 64 , 65 ]. The administration of diets with a varying macronutrient composition shows persistent changes of genes associated with epigenetic mechanisms over generations [ 64 ].
A study by Lian and co-workers [ 65 ] looked into the DNA methylation pattern of flies reared under dietary restriction. Further research looking into DNA methylation pattern in flies under dietary restriction at an older age would therefore provide more valuable data regarding epigenetic modulations. Another possibility to check epigenetic changes is to study chromatin remodeling. In this regard, Sebald and colleagues demonstrated a central role of the chromatin remodeling factor CHD1 on a healthy microbiome composition in the fruit fly [ 67 ], which indirectly indicates an effect of the diet, as it is the most prominent factor affecting the intestinal commensal bacteria [ 68 , 69 ].
This study exemplified the fruit fly as an upcoming model organism in epigenetic research, helping to elucidate diet-dependent effects on the epigenome. In the context of epigenetic research, the fruit fly offers the advantage to investigate epigenetic effects throughout different generations during a relatively short period of time. Other molecules that epigenetically modify gene expression are microRNAs miRNA , small non-coding RNAs with a length of 17—25 nucleotides, normally inhibiting gene expression.
MicroRNAs play a central role in cellular processes such as proliferation, differentiation, and apoptosis, which are known pathways affected in the development of chronic diseases including cancer [ 71 ].
Studies have shown that especially plant bioactives are able to affect miRNA expression which may partly explain their health-promoting properties documented in the development of various chronic inflammatory diseases [ 72 , 73 , 74 ]. Initial experiments identified lin-4 as the first miRNA being essential for the normal development of Ceanorhabditis elegans [ 75 ].
This fact points towards an important input in elucidating miRNA-based processes [ 71 ]. The proteome is defined as the protein complement that is present in a cell, an organ, or an organism at a given time [ 54 , 77 ]. Li and co-workers demonstrated a change in the midgut proteome of the fruit fly receiving the Bowman-Birk protease inhibitor via their diet [ 78 ].
In comparison to control diet-fed animals, the proteomic analysis in fly larvae exposed to this inhibitor showed an impaired expression of proteins associated with protein degradation and transport, as well as fatty acid catabolism [ 78 ].
Another study investigated the effect of dietary ethanol on the proteome of fruit flies. Admittedly, the authors have only focused on short-term effects of the applied compound with the intention to confirm the so-called Hamburger effect, which has been suggested for human proteomes following the consumption of one single hamburger [ 80 ]. In addition, antimicrobial peptides, including metchnikowin, diptericin, attacins, cecropinA1, and drosocin, have been widely used as biomarkers for the Drosophila melanogaster immune system, playing a crucial role in the defense mechanisms, the stem cell proliferation, and the regulation of the gut microbiota in mammals [ 47 ].
The identification and quantification of different antimicrobial peptides by mass spectrometry technologies and gel electrophoresis, as well as their expression levels using qRT-PCR and NGS, may be evaluated to get information on the health status and especially on the immune status of Drosophila melanogaster receiving different diets or supplements such as bioactive compounds.
Altered anti-microbial peptide levels have been related to an impaired proliferation of ISC and intestinal bacterial loads. In particular, an increased expression of the antimicrobial peptides drosocin and cecropin A1 in the intestine has been connected with a prolonged life span of flies [ 81 ].
This increased expression of drosocin and cecropin A1 is associated with a lower activation of the classical immune pathways in the midgut of these flies, such as the immune deficiency IMD and Janus kinase-signal transducers and activators of transcription JAK-STAT pathway, as well as with lower activities of c-Jun N-terminal kinase JNK and epidermal growth factor EGF which points towards a better regeneration and maintenance of ISC and an alleviated stress response [ 81 ].
In a recent publication, Hanson and colleagues [ 82 ] used flies lacking all 14 antimicrobial peptides, that have been systematically tested for their effects on Gram-positive and Gram-negative bacteria and fungi. The Drosophila antimicrobial peptides mainly affect Gram-negative bacteria and represent rather effectors than regulators of the innate immune system in the fruit fly [ 82 ]. Effectors are built in an immune reaction with an antigen while regulators mainly repress ongoing immune reactions.
Methods to detect alterations of the proteome include a methods to separate the proteins and b methods to identify and characterize the proteins. Extractions, precipitations, chromatography, electrophoresis, and centrifugation can be applied to separate the proteins, while mass spectrometry, nuclear magnetic resonance NMR spectroscopy, and immune labeling can be used for protein identification and characterization.
The gut microbiota in the fruit fly can be isolated after the dissection of the gut or from the whole fly [ 23 ]. By using the whole fly, usually, the surface is disinfected by ethanol in order to remove external bacteria.
In addition, a non-invasive approach can be applied by collecting and analyzing fecal spots that have been deposited by the flies during a defined period [ 83 ].
This offers the advantage of analyzing microbiota dynamics in the same cohort at several time points, like throughout a life span experiment or nutritional interventions. As far as we know, there are only a few studies available in Drosophila melanogaster that have analyzed the microbiota composition after applying a specific diet or a specific dietary compound.
Recently, Erkosar et al. The bacterial diversity and alterations in microbiota dynamics in the fruit fly can be analyzed by using 16S rRNA gene sequencing by different methodologies, such as a qPCR approach with species-specific oligonucleotide primer pairs [ 83 ], deep gene sequencing approaches using sequencing [ 38 ] or whole-genome shotgun sequencing [ 86 ], and high-sensitive NanoString nCounter technology for targeted RNA, DNA, or proteins [ 87 ].
Initial data also point towards the use of flow cytometric microbiome analysis as an easy-to-use and cost-effective method to unravel effects on the Drosophila microbiota. Although this method does not deliver direct phylogenetic information, it provides information about relative subcommunity abundance and absolute cell numbers at-line through distinct light scatter and fluorescence properties [ 88 ]. Staats and colleagues have already used a flow cytometry-based analysis together with the sequencing of the V1-V2 regions of the 16S rRNA to detect changes in the microbiome of Drosophila melanogaster following the intake of the plant bioactive ursolic acid [ 85 ].
Drosophila melanogaster has also been demonstrated to be a successful in vivo model system to elucidate the mechanisms of probiotic organisms in the human microbiota i. Therefore, elucidating potential molecular pathways of probiotics or its corresponding metabolites by using the fruit fly as a model organism would help to improve therapies for human diseases related to the energy metabolism, such as obesity and diabetes. Metabolomics is referred to a systematic study of detectable small molecules deriving from specific cellular processes in an organism [ 54 ].
The main technologies applied in metabolomics research are mass spectrometry and NMR spectroscopy, both having advantages and disadvantages [ 59 ]. Drosophila melanogaster is a well-known model in the context of metabolomics research [ 91 , 92 ].
However, studies in the context of diet-metabolome interaction are currently very limited. Curr Med Chem. Ten generations of Drosophila melanogaster reared axenically on a fatty acid-free holidic diet.
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