# Multi-Omics Mechanism of Chronic Gout Arthritis and Discovery of the Thyroid Hormone–AMPK–Taurine Metabolic Axis

## TL;DR

This study uses multi-omics to uncover key proteins and metabolites involved in the progression from acute to chronic gout, identifying a metabolic axis and immune changes that could help in early diagnosis and treatment.

## Contribution

The study introduces a novel multi-omics approach to reveal a thyroid hormone–AMPK–taurine metabolic axis and immune shifts in chronic gout development.

## Key findings

- Nine persistently dysregulated proteins and 11 altered metabolites were identified during the transition from acute to chronic gout.
- Key pathways like thyroid hormone synthesis, AMPK signaling, and taurine metabolism are significantly perturbed in chronic gout.
- Immune response shifts from acute activation to chronic inflammation during the progression of gout.

## Abstract

What are the main findings?
Multi-omics profiling reveals nine persistently dysregulated proteins and 11 consistently altered metabolites during the transition from acute to chronic gouty arthritis.Chronic gout development involves significant perturbations in key pathways—thyroid hormone synthesis, AMPK signaling, and taurine metabolism—and a concomitant shift in the immune response from acute activation to chronic inflammation.

Multi-omics profiling reveals nine persistently dysregulated proteins and 11 consistently altered metabolites during the transition from acute to chronic gouty arthritis.

Chronic gout development involves significant perturbations in key pathways—thyroid hormone synthesis, AMPK signaling, and taurine metabolism—and a concomitant shift in the immune response from acute activation to chronic inflammation.

What are the implications of the main finding?
The study identifies a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and immune microenvironment remodeling as central to chronic gout progression.These findings offer potential targets for early diagnosis and targeted interventions to prevent irreversible joint damage in chronic gouty arthritis.

The study identifies a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and immune microenvironment remodeling as central to chronic gout progression.

These findings offer potential targets for early diagnosis and targeted interventions to prevent irreversible joint damage in chronic gouty arthritis.

The acute gouty arthritis (AGA) to chronic gouty arthritis (CGA) transition is a critical phase leading to irreversible joint damage and systemic complications. However, current molecular mechanism investigations have remained limited to single-omics approaches that lack comprehensive multi-omics explorations. We integrate high-depth data-independent acquisition (DIA) proteomics and untargeted metabolomics to analyze serum samples from healthy controls (n =28), AGA (n = 31), and CGA (n = 14) patients to address this gap. Through differential expression analysis, we identified nine persistently dysregulated pivotal proteins with robust discriminative capacity, including the urate excretion regulator ZBTB20 and inflammation/immune-related proteins (GUCY1A2, CNDP1, LYZ, SERPINA5, GSN). Additionally, 11 consistently altered core metabolites with diagnostic potential were detected, indicating perturbations in sex hormones, thyroid hormones, gut microbiota-derived metabolites, environmental exposures, and nutritional factors. Multi-omics KEGG enrichment analysis highlighted thyroid hormone synthesis, AMPK signaling pathway, and taurine and hypotaurine metabolism as central pathways. Correlation network analysis further revealed significant immune dysregulation, illustrating an evolution from acute immune activation to chronic inflammation during AGA-to-CGA progression. Our study establishes that a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and concomitant immune microenvironment remodeling is associated with chronic gout development. These findings provide critical targets for developing early diagnostic indicators and targeted interventions for CGA.