Gut Microbiome

Butyrate Alleviates Hyperuricemia by Selectively Targeting the Metronidazole/Neomycin-Sensitive Bacterium Dubosiella newyorkensis.

TL;DR

Dubosiella newyorkensis (Dn), identified through selective antibiotic screening, alleviates hyperuricemia by reducing uric acid production, improving renal function, modulating gut microbiota composition, and regulating uric acid transporter expression.

Key Findings

Selective antibiotic screening identified Dubosiella newyorkensis as a metronidazole/neomycin-sensitive bacterium with therapeutic potential against hyperuricemia.

  • Antibiotic-treated mouse models were used to screen gut microbiota components relevant to HUA intervention.
  • The Dubosiella-type strain Dubosiella newyorkensis (Dn) was identified as an effective intervention candidate through this selective antibiotic screening approach.
  • Dn was characterized as sensitive to metronidazole and neomycin, allowing its selective targeting.

Dubosiella newyorkensis treatment significantly reduced uric acid production in hyperuricemic mouse models.

  • Dn treatment led to significant reductions in uric acid (UA) levels compared to untreated hyperuricemic controls.
  • Renal function markers were improved following Dn intervention.
  • Oxidative stress markers were decreased with Dn treatment.
  • Histopathological evaluation confirmed restoration of glomerular atrophy, tubular dilation, and collagen deposition induced by HUA.

Dubosiella newyorkensis modulated gut microbiota composition by enriching beneficial bacteria while suppressing pathobionts.

  • Dn treatment enriched Bacteroides and Romboutsia in the gut microbiota.
  • Dn suppressed the pathobiont Thomasclavelia.
  • These microbiota changes were associated with enhanced production of short-chain fatty acids including acetate, propionate, and butyrate.
  • Butyrate intervention was used alongside antibiotic-treated mouse models to investigate gut microbiota modulation in HUA.

Dubosiella newyorkensis regulated the expression of uric acid transporters to promote uric acid excretion.

  • Molecular analyses demonstrated that Dn downregulated the expression of URAT1, a uric acid reabsorption transporter.
  • Dn upregulated ABCG2, a uric acid efflux transporter, thereby promoting UA excretion.
  • This dual regulation of transporter expression represents a mechanistic basis for the uric acid-lowering effect of Dn.

Dubosiella newyorkensis restored hyperuricemia-induced renal histopathological damage.

  • Histopathological evaluation confirmed that Dn reversed glomerular atrophy caused by HUA.
  • Tubular dilation induced by HUA was restored following Dn treatment.
  • Collagen deposition associated with HUA-induced renal injury was reduced by Dn intervention.

Dubosiella newyorkensis was identified as a promising multitarget therapeutic agent acting on uric acid production, excretion, gut microbiota composition, and renal pathology simultaneously.

  • Dn demonstrated effects on multiple therapeutic targets: UA production reduction, transporter regulation (URAT1 and ABCG2), microbiota modulation, and renal histopathology restoration.
  • The study provides a scientific foundation for microbiome-based strategies against HUA.
  • The findings suggest Dn as a novel probiotic-type intervention for hyperuricemia and gout.

What This Means

This research suggests that a specific gut bacterium called Dubosiella newyorkensis (Dn) can help treat hyperuricemia—a condition where uric acid builds up in the blood, which is the main cause of gout. The researchers discovered this bacterium by using antibiotics to selectively eliminate certain gut bacteria in mice and observing the effects on uric acid levels. They found that Dn works through multiple mechanisms: it lowers uric acid production, helps the kidneys excrete more uric acid by adjusting the activity of key transport proteins (reducing URAT1, which retains uric acid, and increasing ABCG2, which expels it), and also shifts the gut bacterial community toward a healthier balance with more beneficial bacteria and fewer harmful ones. The beneficial changes in gut bacteria driven by Dn also led to increased production of short-chain fatty acids—particularly acetate, propionate, and butyrate—which are compounds known to support gut and metabolic health. Additionally, Dn treatment reversed kidney damage seen in hyperuricemic mice, including abnormalities in kidney structure such as shrunken filtering units, dilated tubules, and excess collagen buildup, while also reducing oxidative stress and improving overall kidney function markers. This research suggests that targeting the gut microbiome, specifically by introducing or promoting Dubosiella newyorkensis, could be a promising new strategy for managing hyperuricemia and potentially gout. Unlike single-target drug treatments, Dn appears to address the condition from multiple angles simultaneously—affecting uric acid metabolism, kidney function, and gut health—laying groundwork for future development of microbiome-based therapies for this common metabolic disorder.

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Citation

Cheng X, Lei Y, Zhang S, Chen L, Wang Y. (2026). Butyrate Alleviates Hyperuricemia by Selectively Targeting the Metronidazole/Neomycin-Sensitive Bacterium Dubosiella newyorkensis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.5c13934