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Phytochemical Intervention Elicits Sex-Specific Responses in the Gut Microbiome and Transcriptome of Drosophila

ABSTRACT: Dietary phytochemicals are plant-derived bioactive compounds that can influence host physiology and gut microbial communities. However, the structural distinctiveness of phytochemicals and their modulation of host intestinal gene expression in a sex-dependent manner remain poorly understood. In this study, we used Drosophila melanogaster to investigate gut transcriptomic responses to four phytochemical-enriched diets, capsaicin, curcumin, resveratrol, and thymoquinone. Two-day-old mated female and male flies were exposed to control or phytochemical-supplemented diets for 10 days, after which gut tissues were dissected for bulk RNA sequencing. Transcriptomic analysis revealed that biological sex was a major source of variation in the gut, with female and male flies showing distinct expression profiles across dietary treatments. Phytochemical supplementation induced compound and sex-specific transcriptional responses. Curcumin produced the strongest transcriptional response, with females showing reduced expression of genes involved in carbohydrate digestion and trehalose metabolism, whereas males showed enrichment of xenobiotic detoxification pathways dominated by cytochrome P450 genes. Capsaicin also induced sex-dependent responses, including detoxification-associated transcriptional changes in females and increased expression of immune-related genes in males. These results indicate that dietary phytochemicals elicit sex-specific gut transcriptomic responses in Drosophila melanogaster and highlight biological sex as an important variable in studies of diet-host interactions.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE330166 | GEO | 2026/05/11

REPOSITORIES: GEO

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Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARï¡ activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Experiment Overall Design: Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0â¢2% curcumin or control + 0â¢1% rutin and monitored from the age of 7 to 24 weeks. As only curcumin significantly reduced colonic HIS, comparison of the gene expression levels in colon was carried out using total RNA from colon tissue of four mdr1a-/- mice from the control group (high HIS) and four mdr1a-/- mice from the curcumin group (low HIS). A reference design with eight arrays was used for this comparison, where each individual RNA sample was hybridized in the array with the reference RNA, totalizing 4 biological replicates per treatment.

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Phytochemical Intervention Elicits Sex-Specific Responses in the Gut Microbiome and Transcriptome of Drosophila

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