Drosophila melanogaster as a model organism for intestinal function research in the context of bioactive plant-derived compounds

Drosophila melanogaster (D. melanogaster, fruit fly) is a promising model organism to research intestinal functions in healthy and pathological states. Abundant gene homology, as well as anatomical and physiological similarities of the fruit fly’s and human’s intestine make the fruit fly a suitable model for the research of bioactive plant-derived compounds and intestinal health. The aim of this doctoral thesis was to establish a method of compound bioavailability evaluation in D. melanogaster and to apply the fruit fly in the research of the effects of selected plant extracts (soybean germs, citrus fruits, grape seeds, mixed wood barks) on intestinal barrier integrity, counteraction to the intestinally induced stresses, lifespan, metabolism and further bioactivity markers.

In this doctoral thesis, a pharmacokinetic research method of compound retention quantification (CORE) in D. melanogaster was introduced. Applying this method to study isoflavone pharmacokinetics, it was shown that female fruit flies retain significantly more isoflavones than male flies, with both sexes retaining more isoflavones administered in micellized physicochemical form compared to water-based solution. The results indicated that the higher fraction of the retained isoflavones in females positively correlated with stronger metabolic changes. At the same time, a lower fraction of the retained isoflavones in males could be connected to a significantly upregulated expression of the multidrug resistance protein gene Mrp50.

Next, D. melanogaster was applied in the comparative bioactivity study of the non-fermented and biotransformed (hydrolyzed and fermented) citrus fruit extracts. Here, fractions of the dextran sulfate sodium (DSS) induced intestinal barrier-damaged flies, dead flies, as well as reactive oxygen species (ROS) levels were investigated. It was demonstrated that citrus extract biotransformed with citric acid hydrolysis and Lactiplantibacillus plantarum could significantly reduce intestinal barrier damage, ROS levels, and stressor-related mortality amongst the fruit flies in a concentration-dependent manner.

The protective properties of the grape seed extract were tested in the aging D. melanogaster. For that, the population of the fruit flies was naturally aged on food with reduced dietary fiber content with or without grape seed extract treatment. Twice a week test flies were placed on the same feed with the addition of the blue dye to screen for intestinal barrier dysfunction. The results indicated that grape seed extract significantly reduced the fraction of the aging flies with the disrupted intestinal barrier and increased the maximal lifespan in the treated populations compared to the control group.

Finally, the effect of the lignan-rich wood extracts on the intestinal barrier integrity was investigated in D. melanogaster as a part of the feed additive development trial. The fruit flies were intestinally challenged with DSS and simultaneously treated with the tested wood extracts. Similar to the results of the in vitro experiments, wood extracts improved the intestinal barrier integrity and reduced the fraction of the fruit flies with the intestinal barrier rupture, as well as mortality in the treated groups. The results of this study were implemented in a follow-up piglet feeding trial.