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Glutamine Flux Imaging Using Genetically Encoded Sensors
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Glutamine Flux Imaging Using Genetically Encoded Sensors

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The Negative Feedback of the Glutamine/Prostatitis Loop Identified Among 1400 Metabolites and Prostatitis via

Yi Wang1,2, Hao Ji3, Yingfei Chen2

  • 1Department of Urology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.

Mediators of Inflammation
|July 23, 2025
PubMed

Insights

This study used Mendelian randomization to identify four metabolic causes and two metabolic phenotypes of prostatitis. A negative feedback loop between glutamine and prostatitis was also discovered, offering new therapeutic targets.

Area of Science:

  • Metabolomics
  • Genetics
  • Urology

Background:

  • Prostatitis presents diagnostic and therapeutic challenges due to unclear causes and high recurrence rates.
  • Understanding the metabolic underpinnings of prostatitis is crucial for identifying novel treatment strategies.

Purpose of the Study:

  • To investigate the causal relationships between 1400 metabolites and prostatitis using Mendelian randomization.
  • To identify potential metabolic etiologies and phenotypes associated with prostatitis.
  • To uncover novel therapeutic targets for prostatitis.

Main Methods:

  • Two-sample Mendelian randomization analysis was performed using data from FinnGen and GWAS Catalog.
  • Sensitivity analyses including heterogeneity, pleiotropy, and leave-one-out analyses were conducted to ensure robustness.

Main Results:

  • Four metabolic etiologies for prostatitis were identified: glutamine degradant levels, adenosine 5'-monophosphate (AMP)-inosine 5'-monophosphate (IMP) ratio, glycolithocholate-glycolithocholate sulfate ratio, and AMP-citrate ratio.
  • Genetic predisposition to lower glutamine degradant levels, AMP-IMP ratio, or glycolithocholate-glycolithocholate sulfate ratio decreased prostatitis risk, while higher AMP-citrate ratio increased risk.
  • Two metabolic phenotypes, glutamine degradant and histidine betaine (hercynine) levels, were associated with prostatitis, and a negative feedback loop between glutamine and prostatitis was observed.

Conclusions:

  • This study identified four metabolic etiologies and two metabolic phenotypes for prostatitis in the European population.
  • A novel negative feedback loop between glutamine metabolism and prostatitis was discovered.
  • These findings offer potential new therapeutic targets for prostatitis management.
Keywords:
Mendelian randomizationclinical implicationsmetabolitesnegative feedback loopprostatitis

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