Dataset Information

The POU/Oct Transcription Factor Pdm1/nub Is Necessary for a Beneficial Gut Microbiota and Normal Lifespan of Drosophila.

ABSTRACT: Maintenance of a stable gut microbial community relies on a delicate balance between immune defense and immune tolerance. We have used Drosophila to study how the microbial gut flora is affected by changes in host genetic factors and immunity. Flies with a constitutively active gut immune system, due to a mutation in the POU transcriptional regulator Pdm1/nubbin (nub) gene, had higher loads of bacteria and a more diverse taxonomic composition than controls. In addition, the microbial composition shifted considerably during the short lifespan of the nub1 mutants. This shift was characterized by a loss of relatively few OTUs (operational taxonomic units) and a remarkable increase in a large number of Acetobacter spp. and Leuconostoc spp. Treating nub1 mutant flies with antibiotics prolonged their lifetime survival by more than 100%. Immune gene expression was also persistently high in the presence of antibiotics, indicating that the early death was not a direct consequence of an overactive immune defense but rather an indirect consequence of the microbial load and composition. Thus, changes in host genotype and an inability to regulate the normal growth and composition of the gut microbiota leads to a shift in the microbial community, dysbiosis and early death.

SUBMITTER: Dantoft W

PROVIDER: S-EPMC6738862 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The POU/Oct Transcription Factor Pdm1/nub Is Necessary for a Beneficial Gut Microbiota and Normal Lifespan of Drosophila.

Dantoft Widad W Lundin Daniel D Esfahani Shiva Seyedoleslami SS Engström Ylva Y

Journal of innate immunity 20160528 4

Maintenance of a stable gut microbial community relies on a delicate balance between immune defense and immune tolerance. We have used Drosophila to study how the microbial gut flora is affected by changes in host genetic factors and immunity. Flies with a constitutively active gut immune system, due to a mutation in the POU transcriptional regulator Pdm1/nubbin (nub) gene, had higher loads of bacteria and a more diverse taxonomic composition than controls. In addition, the microbial composition ...[more]

PMID: 27231014

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Project description:BackgroundA number of cellular processes have evolved in metazoans that increase the proteome repertoire in relation to the genome, such as alternative splicing and translation recoding. Another such process, translational stop codon readthrough (SCR), generates C-terminally extended protein isoforms in many eukaryotes, including yeast, plants, insects, and humans. While comparative genome analyses have predicted the existence of programmed SCR in many species including humans, experimental proof of its functional consequences are scarce.ResultsWe show that SCR of the Drosophila POU/Oct transcription factor Ventral veins lacking/Drifter (Vvl/Dfr) mRNA is prevalent in certain tissues in vivo, reaching a rate of 50% in the larval prothoracic gland. Phylogenetically, the C-terminal extension is conserved and harbors intrinsically disordered regions and amino acid stretches implied in transcriptional activation. Elimination of Vvl/Dfr translational readthrough by CRISPR/Cas9 mutagenesis changed the expression of a large number of downstream genes involved in processes such as chromatin regulation, neurogenesis, development, and immune response. As a proof-of-principle, we demonstrate that the C-terminal extension of Vvl/Dfr is necessary for correct timing of pupariation, by increasing the capacity to regulate its target genes. The extended Vvl/Dfr isoform acts in synergy with the transcription factor Molting defective (Mld) to increase the expression and biosynthesis of the steroid hormone ecdysone, thereby advancing pupariation. Consequently, late-stage larval development was prolonged and metamorphosis delayed in vvl/dfr readthrough mutants.ConclusionsWe demonstrate that translational recoding of a POU/Oct transcription factor takes place in a highly tissue-specific and temporally controlled manner. This dynamic and regulated recoding is necessary for normal expression of a large number of genes involved in many cellular and developmental processes. Loss of Vvl/Dfr translational readthrough negatively affects steroid hormone biosynthesis and delays larval development and progression into metamorphosis. Thus, this study demonstrates how SCR of a transcription factor can act as a developmental switch in a spatiotemporal manner, feeding into the timing of developmental transitions between different life-cycle stages.

Project description:Woody biomass is a sustainable and virtually unlimited source of hemicellulosic polysaccharides. The predominant hemicelluloses in softwood and hardwood are galactoglucomannan (GGM) and arabinoglucuronoxylan (AGX), respectively. Based on the structure similarity with common dietary fibers, GGM and AGX may be postulated to have prebiotic properties, conferring a health benefit on the host through specific modulation of the gut microbiota. In this study, we evaluated the prebiotic potential of acetylated GGM (AcGGM) and highly acetylated AGX (AcAGX) obtained from Norwegian lignocellulosic feedstocks in vitro In pure culture, both substrates selectively promoted the growth of Bifidobacterium, Lactobacillus, and Bacteroides species in a manner consistent with the presence of genetic loci for the utilization of ?-manno-oligosaccharides/?-mannans and xylo-oligosaccharides/xylans. The prebiotic potential of AcGGM and AcAGX was further assessed in a pH-controlled batch culture fermentation system inoculated with healthy adult human feces. Results were compared with those obtained with a commercial fructo-oligosaccharide (FOS) mixture. Similarly to FOS, both substrates significantly increased (P?<?0.05) the Bifidobacterium population. Other bacterial groups enumerated were unaffected with the exception of an increase in the growth of members of the Bacteroides-Prevotella group, Faecalibacterium prausnitzii, and clostridial cluster IX (P?<?0.05). Compared to the other substrates, AcGGM promoted butyrogenic fermentation whereas AcAGX was more propiogenic. Although further in vivo confirmation is necessary, these results demonstrate that both AcGGM and AcAGX from lignocellulosic feedstocks can be used to direct the promotion of beneficial bacteria, thus exhibiting a promising prebiotic ability to improve or restore gut health.IMPORTANCE The architecture of the gut bacterial ecosystem has a profound effect on the physiology and well-being of the host. Modulation of the gut microbiota and the intestinal microenvironment via administration of prebiotics represents a valuable strategy to promote host health. This work provides insights into the ability of two novel wood-derived preparations, AcGGM and AcAGX, to influence human gut microbiota composition and activity. These compounds were selectively fermented by commensal bacteria such as Bifidobacterium, Bacteroides-Prevotella, F. prausnitzii, and clostridial cluster IX spp. This promoted the microbial synthesis of acetate, propionate, and butyrate, which are bene?cial to the microbial ecosystem and host colonic epithelial cells. Thus, our results demonstrate potential prebiotic properties for both AcGGM and AcAGX from lignocellulosic feedstocks. These findings represent pivotal requirements for rationally designing intervention strategies based on the dietary supplementation of AcGGM and AcAGX to improve or restore gut health.

Dataset Information

The POU/Oct Transcription Factor Pdm1/nub Is Necessary for a Beneficial Gut Microbiota and Normal Lifespan of Drosophila.

Publications

The POU/Oct Transcription Factor Pdm1/nub Is Necessary for a Beneficial Gut Microbiota and Normal Lifespan of Drosophila.

Similar Datasets

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