Dataset Information

A mitochondrial sirtuin shapes the intestinal microbiota by controlling lysozyme expression

ABSTRACT: Sirtuins are sensors that orchestrate cellular responses to adapt to changing situations. Here, we show that a protein-restricted diet induces strongly induces increased intestinal expression of the sole Drosophila mitochondrial sirtuin, dSirt4. To elucidate the effects of deregulated dSirt4 expression in the intestine, we analyzed dSirt4-deficient animals. These dSirt4-deficient flies show substantial changes in their intestine's intestinal proteome and their physiological properties. One of the most striking effects was the strong induction of lysozyme gene expression in the intestine, which was also matched by increased lysozyme activity. This effect was organ-autonomous, as it was also observed in flies in which dSirt4 was knocked down only in the intestinal enterocytes. This significantly increased lysozyme expression in response to dSirt4 downregulation did not reduce the total number of bacteria in the gut, but rather shifted the composition of the microbiota by reducing the number of gram-positive bacteria. This effect on microbiota composition can be attributed to dSirt4-dependent lysozyme expression, as it is absent in a lysozyme-deficient background. dSirt4 deficiency in the enterocytes shortened the lifespan of the flies, which was also observed in flies with ectopic lysozyme overexpression in the enterocytes. We assume that high lysozyme expression leads to a dysbiotic state of the microbiota associated with a shortened lifespan.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Intestine

SUBMITTER: Andreas Tholey

LAB HEAD: Andreas Tholey

PROVIDER: PXD054704 | Pride | 2025-06-23

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	DrosophSirt4_1DLC_LFQ.pdResult	Other
	Drosophila_20210723170125_CD.raw	Raw
	Drosophila_20210724015207_CD.raw	Raw
	Drosophila_20210724044927_CD.raw	Raw
	Drosophila_20210724084855_CD.raw	Raw

Items per page:

1 - 5 of 23

Publications

Mitochondrial sirtuin 4 shapes the intestinal microbiota of Drosophila by controlling lysozyme expression.

Knop Mirjam M Treitz Christian C Bettendorf Stina S Bossen Judith J von Frieling Jakob J Doms Shauni S Saboukh Abdulgawaad A Bruchhaus Iris I Kühnlein Ronald P RP Baines John F JF Tholey Andreas A Roeder Thomas T

Animal microbiome 20250613 1

<h4>Background</h4>Sirtuins are deacetylases that are highly conserved throughout the animal kingdom. They act as metabolic sensors that coordinate cellular responses, allowing an adapted response to various stressors. Epithelial cells, especially those of the intestine, are directly exposed to a wide range of stressors. Together with the microbiota, they form a complex ecosystem with mutual influences. The significance of sirtuins in this complex system is still waiting to be clarified.<h4>Resu ...[more]

PMID: 40514757

Similar Datasets

Project description:Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called âintestinal barrier proteinsâ. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPARÎ±), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPARÎ± on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPARÎ±-null mice. Treatment with the synthetic PPARÎ± agonist WY14643 served as reference. Results: We identified 74 barrier genes that were PPARÎ±-dependently regulated 6 hours after activation with WY14643. For eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and oleic acid (OA) these numbers were 46, 41, and 19, respectively. The overlap between EPA-, DHA-, and WY14643-regulated genes was considerable, whereas OA treatment showed limited overlap. Functional implications inferred form our data suggested that nutrient-activated PPARÎ± regulated transporters and phase I/II metabolic enzymes were involved in a) fatty acid oxidation, b) cholesterol, glucose, and amino acid transport and metabolism, c) intestinal motility, and d) oxidative stress defense. Conclusion: We identified intestinal barrier genes that were PPARÎ±-dependently regulated after acute activation by fatty acids.This knowledge provides a better understanding of the impact dietary fat has on the barrier function of the gut, identifies PPARÎ± as an important factor controlling this key function, and underscores the importance of PPARÎ± for nutrient-mediated gene regulation in intestine. Experiment Overall Design: Pure bred wild-type (129S1/SvImJ) and PPARÎ±-null (129S4/SvJae) mice were treated for 6 hours with the synthetic triacylglycerols triolein [oleic acid (OA, C18:1)], trieicosapentaenoin [eicosapentaenoic acid (EPA, C20:5)] or tridocosahexaenoin [ocosahexaenoic acid (DHA, C22:6)], or the potent PPARÎ± agonist WY14,643. Two weeks before the start of the experiment, mice were put on a modified AIN76A diet, in which corn oil was replaced by olive oil. At the day of the experiment mice were fasted for four hours. At 9 AM mice were dosed by oral gavage with 400 Âµl of a 0.1% WY14643 suspension in 0.5% carboxymethyl cellulose, or 400 Âµl of the synthetic triacylglycerols. Six hours after the gavage the mice were anaesthetized, small intestines were removed, flushed with ice-cold PBS and remaining fat and pancreatic tissue was carefully removed. Total RNA was then isolated. RNA of 4-5 biological replicates was hybridized to Affymetrix 430-2.0 plus arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.