| Title: | Allostatic load elevates the risk and adverse prognosis of immune-mediated inflammatory diseases: modulatory effects of lifestyle interventions and genetic susceptibility |
| Journal: | The journal of nutrition health & aging |
| Published: | 24 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41581336/ |
| DOI: | https://doi.org/10.1016/j.jnha.2026.100792 |
Publication 18476
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Abstract
BACKGROUND: Allostatic load (AL)-the cumulative biological cost of lifelong stress-can disrupt immune homeostasis via hypothalamic-pituitary-adrenal-axis dysregulation and persistent sympathetic activation. Immune-mediated inflammatory diseases (IMIDs) are organ-specific chronic inflammatory disorders imposing a major public-health burden, yet their causal link with AL remains unclear.</p>
METHODS: In this prospective study of 186 310 UK Biobank participants, Cox proportional-hazards models quantified dose-response associations between AL and the incidence of ten IMIDs plus all-cause mortality. Interaction models evaluated the modifying effects of physical activity, ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and other lifestyle variables, and assessed gene-environment interplay using polygenic risk scores (PRS).</p>
RESULTS: Compared with the lowest AL quartile, the highest quartile showed significantly greater incidence of rheumatoid arthritis (hazard ratios (HR) = 1.52), spondyloarthritis (HR = 2.50), asthma (HR = 1.38), inflammatory bowel disease (IBD) (HR = 1.19), type 1 diabetes (T1DM) (HR = 5.16), psoriasis (HR = 1.87), autoimmune retinopathy (HR = 1.77) and composite IMIDs (HR = 1.55) (all p < 0.05). Elevated AL also predicted dose-dependent increases in all-cause mortality among patients with rheumatoid arthritis (HR = 6.59), asthma (HR = 1.87), IBD (HR = 2.00), T1DM (HR = 2.72) and composite IMIDs (HR = 2.01). Sufficient physical activity and higher ω-3 PUFA intake partially attenuated AL-related risks, whereas high PRS synergistically amplified AL effects for spondyloarthritis (attributable proportion (AP) = 7.6%), T1DM (AP = 4.7%) and psoriasis (AP = 4.9%).</p>
CONCLUSIONS: AL is causally linked to both the development and prognosis of IMIDs, with its impact jointly modifiable by lifestyle factors and genetic susceptibility. Building AL-centred psychoneuroimmunological biomarker networks may enable refined risk stratification and precision interventions for IMIDs.</p>
5 Authors
- Ziling Yang
- Jinming Zhang
- Zhong Qu
- Zhuo Zhao
- Yajuan Zheng
1 Application
| Application ID | Title |
|---|---|
| 84347 | Integration of clinical data and genomic data to construct diagnosis and prognosis system for digestive diseases and related complications |
Enabling scientific discoveries that improve human health