Dataset Information

Eurotium cristatum ameliorates hyperuricemia-induced renal pyroptosis through microbiome-derived metabolome reprogramming.

ABSTRACT: Fermented foods harbor beneficial microbes that support gut health and metabolic balance, offering natural probiotic strategies for managing conditions such as hyperuricemia through modulation of the gut microbiota and their derived metabolites. We demonstrate that Eurotium cristatum (E. cris), a dominant probiotic fungus in Fu brick tea, can directly utilize uric acid (UA) as a carbon source and ameliorate hyperuricemia progression by reprogramming the gut microbiome and metabolome, thereby alleviating NLRP3-mediated inflammation and pyroptosis in renal tissues. Oral administration of E. cristatum in hyperuricemic mice upregulated the expression of ATP-binding cassette subfamily G member 2 (ABCG2) in both the kidney and intestine, as well as the intestinal tight junction protein ZO-1, suggesting enhanced UA excretion and maintenance intestinal permeability. Microbiota analysis revealed that E. cristatum reversed dysbiosis by enriching beneficial bacteria (Coprococcus, Ruminococcus) while reducing pathogenic taxa (Turicibacteraceae, Clostridiaceae). Correlation analyses further indicated that these changes were linked to the restoration of the host's co-metabolite profile, characterized by enhanced purine degradation (decreased xanthine/hypoxanthine) and control amino acid metabolism (regulation of the urea cycle, histidine metabolism and the branched-chain amino acid pathway), which synergistically promoted UA clearance and reduced systemic metabolic burden. Notably, fecal microbiota transplantation in the intervention group replicated these effects, confirming that these benefits depend on the remodeling of the microbiota. Furthermore, we confirmed that the microbiome remodeling induced by E. cristatum improved the urea cycle, histidine metabolism and contributed to the suppression of renal macrophage infiltration and NLRP3/GSDMD-mediated pyroptosis. In summary, this study elucidates how a food-derived probiotic fungus reshapes the gut microbiota and its metabolome to provide renal protection by promoting UA catabolism, the urea cycle and histidine metabolism, thereby offering new perspectives for probiotic intervention strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE344441 | GEO | 2026/08/25

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Fermented foods harbor beneficial microbes that support gut health and metabolic balance, offering natural probiotic strategies for managing conditions such as hyperuricemia through modulation of the gut microbiota and their derived metabolites. We demonstrate that Eurotium cristatum (E. cris), a dominant probiotic fungus in Fu brick tea, can directly utilize uric acid (UA) as a carbon source and ameliorate hyperuricemia progression by reprogramming the gut microbiome and metabolome, thereby alleviating NLRP3-mediated inflammation and pyroptosis in renal tissues. Oral administration of E. cristatum in hyperuricemic mice upregulated the expression of ATP-binding cassette subfamily G member 2 (ABCG2) in both the kidney and intestine, as well as the intestinal tight junction protein ZO-1, suggesting enhanced UA excretion and maintenance intestinal permeability. Microbiota analysis revealed that E. cristatum reversed dysbiosis by enriching beneficial bacteria (Coprococcus, Ruminococcus) while reducing pathogenic taxa (Turicibacteraceae, Clostridiaceae). Correlation analyses further indicated that these changes were linked to the restoration of the host's co-metabolite profile, characterized by enhanced purine degradation (decreased xanthine/hypoxanthine) and control amino acid metabolism (regulation of the urea cycle, histidine metabolism and the branched-chain amino acid pathway), which synergistically promoted UA clearance and reduced systemic metabolic burden. Notably, fecal microbiota transplantation in the intervention group replicated these effects, confirming that these benefits depend on the remodeling of the microbiota. Furthermore, we confirmed that the microbiome remodeling induced by E. cristatum improved the urea cycle, histidine metabolism and contributed to the suppression of renal macrophage infiltration and NLRP3/GSDMD-mediated pyroptosis. In summary, this study elucidates how a food-derived probiotic fungus reshapes the gut microbiota and its metabolome to provide renal protection by promoting UA catabolism, the urea cycle and histidine metabolism, thereby offering new perspectives for probiotic intervention strategies.

Project description:Increased plasma uric acid (hyperuricemia) has been associated with worse outcomes for chronic kidney disease (CKD). But some attempts to control uric acid (UA) in large-cohort clinical trials did not produce clinically meaningful benefits for CKD. Some studies suggest that only hyperuricemia with crystals, but not asymptomatic hyperuricemia promotes the progression of CKD. Salt-sensitivity (SS) in blood pressure is a prevalent trait that is sexually dimorphic and results in kidney damage. But the connection between hyperuricemia and SS hypertension (HTN) is still unclear. Here we tested the connection between the two using both male and female Dahl SS rats, a well-establish model of SS HTN. We hypothesized that mild asymptomatic hyperuricemia is beneficial in controlling the progression of SS HTN. A uricase inhibitor, oxonic acid (2%) (Oxo) was used to induce hyperuricemia and high-salt (HS) (4% NaCl) diet was used to induce SS HTN. After 3 weeks, in response to oxonic acid supplementation, both sexes showed a significant increase of UA in plasma compared to their respective HS-only controls (Males: 0.63 ±0.07 vs. 2.17 ±0.34; Females: 0.78 ±0.15 vs. 2.04 ±0.35 mg/dl, HS vs. HS/oxo). Interestingly, only male HS/oxo rats showed a significant increase in uricosuria (Males: 0.23 ±0.03 vs. 0.45 ±0.06; Femaels: 0.26 ±0.06 vs. 0.26 ±0.001 UA/Cre, HS vs. HS/oxo). Moreover, the mild hyperuricemia was associated with a significant attenuation of the progression and magnitude of the mean arterial pressure in male but not female rats (Males: 157 ±3 vs. 136 ±3; Females: 155 ±6 vs. 154 ±5 mmHg, HS vs. HS/oxo). Xanthine oxidase (XO) is one of the enzymes that produce UA, and its activity has been shown to affect HTN as well. Therefore, we examined the level of XO activity in the plasma after the treatment. While there was no difference in the activity based on the diet within each sex, females had significantly lower levels of XO activity compared to males in each of the diets. To further investigate the beneficial phenotype seen in male rats, we evaluate changes in the progression of renal pathology. The HS/oxo group compared to the HS group had a lower kidney weight/body weight ratio and lower protein cast accumulation, indicating lower kidney damage. Furthermore, the HS/Oxo treated males had less oxidative damage in their tubules than the HS-only males. Bulk-RNA seq done on the male kidneys revealed that attenuated HTN phenotype was associated with an increased expression in Mas1 (MAS receptor), Klk-1 (Kallikrein-1), and Pcsk6 (PCSK6 enzyme) which can all lead to the activation of different vasodilatory pathways. Our study showed that in male but not female Dahl SS rats, asymptomatic mild hyperuricemia accompanied by hyperuricosuria ameliorates the progression of SS HTN and protects kidneys from further damage. Thus, our findings challenge the notion of hyperuricemia being inherently detrimental to health and highlight that this is an oversimplified view of UA’s role in disease.

Dataset Information

Eurotium cristatum ameliorates hyperuricemia-induced renal pyroptosis through microbiome-derived metabolome reprogramming.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets