High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17...

Area of Science:

• Immunology
• Gastroenterology
• Urology

Background:

• Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves voiding symptoms and pelvic pain, driven by proinflammatory T helper 17 (Th17) cells.
• High-salt diet (HSD) can induce autoimmune responses via the Th17 cell axis, but its role in CP/CPPS is unclear.

Purpose of the Study:

• To investigate the correlation between HSD and CP/CPPS patient symptoms.
• To explore the impact of HSD on CP/CPPS development and mechanisms in a mouse model.
• To identify potential therapeutic targets for HSD-aggravated CP/CPPS.

Main Methods:

• Clinical evaluation of CP/CPPS patients and analysis of HSD correlation.
• Establishment of an experimental autoimmune prostatitis (EAP) mouse model fed normal-salt diet (NSD) or HSD.
• Gut microbiota and metabolomic analysis, fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation assays.

Main Results:

• HSD correlated positively with CP/CPPS symptoms and worsened prostate inflammation and pain in EAP mice by promoting Th17 cell differentiation.
• HSD reduced beneficial gut bacteria and 5-HIAA levels, exacerbating EAP.
• 5-HIAA supplementation ameliorated HSD-induced EAP symptoms by inhibiting Th17 differentiation, while AHR inhibition reversed this effect, highlighting the 5-HIAA/AHR/SGK1/FOXO1 axis.

Conclusions:

• High salt intake is a risk factor for CP/CPPS, promoting Th17 cell differentiation.
• The 5-HIAA/AHR/SGK1/FOXO1 pathway is implicated in HSD-aggravated CP/CPPS.
• This pathway represents a potential therapeutic target for managing CP/CPPS.