Gut Bacterial Species Distinctively Impact Host Purine Metabolites during Aging in Drosophila

Yamauchi, Teruaki; Oi, Ayano; Kosakamoto, Hina; Akuzawa-Tokita, Yoriko; Murakami, Takumi; Mori, Hiroshi; Miura, Masayuki; Obata, Fumiaki

doi:10.1016/j.isci.2020.101477

Cited by 35 publications

(42 citation statements)

References 49 publications

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“…Yamauchi et al demonstrated how some bacterial species within the gut microbiome could release many metabolites and protein molecules that distinctively impact host purine levels (Yamauchi et al 2020 ). Given that enrichment of Bacteroides may be the footprint of gout disease, our work implied an understanding of the role of Bacteroides species found in the core microbiota of gouty patients.…”

Section: Discussionmentioning

confidence: 99%

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

Méndez-Salazar

Vázquez‐Mellado

Casimiro-Soriguer

et al. 2021

Mol Med

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Objective To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. Methods Hypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. Results We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. Conclusion Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

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Section: Discussionmentioning

confidence: 99%

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

Méndez-Salazar

Vázquez‐Mellado

Casimiro-Soriguer

et al. 2021

Mol Med

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“…A chronic inflammatory condition in aged flies triggers neurodegeneration and shortens lifespan, which can be rescued by inhibition of Imd signalling in glial cells ( Kounatidis et al, 2017 ). Age-related activation of the Imd pathway in the renal (Malpighian) tubules induced by a commensal organism, Acetobacter persici , triggers age-dependent metabolic shifts, including purine metabolism ( Yamauchi et al, 2020 ). These studies have revealed that age-related immune activation in various tissues leads to organismal ageing.…”

Section: Introductionmentioning

confidence: 99%

Activation of innate immunity during development induces unresolved dysbiotic inflammatory gut and shortens lifespan

Yamashita

Kosakamoto

et al. 2021

Disease Models &Amp; Mechanisms

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An early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. Using Drosophila as a model, we find that activation of innate immune pathway Immune deficiency (Imd) signalling in the developing larvae increases adult starvation resistance, decreases food intake and shortens organismal lifespan. Interestingly, lifespan is shortened by Imd activation in the larval gut and fat body, whereas starvation resistance and food intake are altered by that in neurons. The adult flies that developed with Imd activation show sustained Imd activity in the gut, despite complete tissue renewal during metamorphosis. The larval Imd activation increases an immunostimulative bacterial species, Gluconobacter sp., in the gut microbiome, and this dysbiosis is persistent to adulthood. Removal of gut microbiota by antibiotics in the adult fly mitigates intestinal immune activation and rescues the shortened lifespan. This study demonstrates that early-life immune activation triggers long-term physiological changes, highlighted as an irreversible alteration in gut microbiota, prolonged inflammatory intestine and concomitant shortening of the organismal lifespan.

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“…Arc1 regulates lipid homeostasis and central carbon metabolite levels in Drosophila larvae (Mosher et al, 2015), and loss of Arc1 results in enhanced adult starvation resistance (Mattaliano et al, 2007). These and other metabolic traits are also impacted by the microbiota, depending on dietary conditions and host genetic background (Dobson et al, 2015; Gnainsky et al, 2021; Judd et al, 2018; Yamauchi et al, 2020). One major consequence of GF-induced metabolic dysregulation in Drosophila is prolonged larval growth (Strigini and Leulier, 2016).…”

Section: Resultsmentioning

confidence: 99%

Arc1 and the microbiota together modulate growth and metabolic traits inDrosophila

Keith

Bishop

Fallacaro

et al. 2020

Preprint

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Perturbations to animal-associated microbial communities (the microbiota) have deleterious effects on various aspects of host fitness, including dysregulated energy metabolism. However, the molecular processes underlying these microbial impacts on the host are poorly understood. In this study, we identify a novel connection between the microbiota and the neuronal factor Arc1 that affects metabolism and development in Drosophila. We find that Arc1 exhibits tissue-specific microbiota-dependent expression changes, and that flies bearing a null mutation of Arc1 complete larval development at a dramatically slowed rate compared to wild-type animals. In contrast, monoassociation with a single Acetobacter sp. isolate was sufficient to enable Arc1 mutants to develop at a wild-type rate. These developmental phenotypes are highly sensitive to composition of the larval diet, suggesting the growth rate defects of GF flies lacking Arc1 reflect metabolic dysregulation. Additionally, we show that pre-conditioning the larval diet with Acetobacter sp. partially accelerates Arc1 mutant development, but live bacteria are required for the full growth rate promoting effect. Finally, GF Arc1 mutants display multiple traits consistent with reduced insulin signaling activity that are reverted by association with Acetobacter sp., suggesting a potential mechanism underlying the microbe-dependent developmental phenotypes. Our results reveal a novel role for Arc1 in modulating insulin signaling, metabolic homeostasis, and growth rate that is specific to the host’s microbial and nutritional environment.SUMMARYDrosophila Arc1 exhibits microbiota-dependent, tissue-specific differential expression, mitigates the impacts of germ-free rearing on insulin signaling and growth rate, but is dispensable for metabolic homeostasis in Acetobacter-colonized flies.

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Gut Bacterial Species Distinctively Impact Host Purine Metabolites during Aging in Drosophila

Cited by 35 publications

References 49 publications

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

Activation of innate immunity during development induces unresolved dysbiotic inflammatory gut and shortens lifespan

Arc1 and the microbiota together modulate growth and metabolic traits inDrosophila

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