Convergence of Epidemiology and Modifiable Causal Risk Factors in Inflammatory Bowel Disease and Alzheimer’s Disease

Liuxi Chu; Zhongpeng Dai; Sisi Wang; Qiang Li; Wenyuan Wang; Ping Wu; Xun Chen; Jiping Wei; Yuqing Li; Wenjie Hu; Chen Gao; Wenjia Wang; Quan Zhang; Zunyong Feng; Xiaokun Li; Zhouguang Wang

doi:10.15212/bioi-2026-0023

BIO Integration ›› 2026, Vol. 7 ›› Issue (1) :22 DOI: 10.15212/bioi-2026-0023

Original Article

research-article

Convergence of Epidemiology and Modifiable Causal Risk Factors in Inflammatory Bowel Disease and Alzheimer’s Disease

Liuxi Chu ¹^,²^,^a^,^*
, Zhongpeng Dai ³^,^a
, Sisi Wang ¹^,^a
, Qiang Li ⁴^,^a
, Wenyuan Wang ⁵
, Ping Wu ⁶
, Xun Chen ⁶
, Jiping Wei ⁶
, Yuqing Li ⁶
, Wenjie Hu ⁶
, Chen Gao ⁷
, Wenjia Wang ⁷
, Quan Zhang ⁸
, Zunyong Feng ⁶^,^*
, Xiaokun Li ⁶^,^*
, Zhouguang Wang ¹^,⁶^,^*

Author information +

¹ The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325035, Zhejiang, China

² Affiliated Cixi Hospital, Wenzhou Medical University , Ningbo 315300, Zhejiang, China

³State Key Laboratory of Brain and Cognitive Sciences, Laboratory of Neuropsychology & Human Neuroscience, The University of Hong Kong , Hong Kong SAR 999077, China

⁴ Human Anatomy Experimental Training Center, School of Basic Medical Sciences, Wannan Medical College , 241002, Wuhu, Anhui, China

⁵ JiaXing University College of Medicine , Jiaxing 314001, Zhejiang, China

⁶ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University , Wenzhou 325000, China

⁷ State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University , Nanjing 210096, Jiangsu, China

⁸ Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center , Memphis 38163, TN, USA

*Liuxi Chu, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China; Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo 315300, Zhejiang, China, E-mail:clx0605@wmu.edu.cn;

Zunyong Feng, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China, E-mail:fengzy@wmu.edu.cn;

Xiaokun Li, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China, E-mail:xiaokunli@wmu.edu.cn;

Zhouguang Wang, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), National Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China, E-mail:wangzhouguang@wmu.edu.cn

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Abstract

Background: Inflammatory bowel disease (IBD) and Alzheimer’s disease (AD) are major global health burdens that are rising in prevalence but are typically studied as distinct disorders. This study systematically characterizes the convergent risk architecture between IBD and AD using integrated epidemiological, causal, and molecular approaches.

Methods: Global epidemiology, Mendelian randomization (MR), and in silico transcriptomic cross-validation were integrated. Global Burden of Disease 2021 data from 204 countries (1990–2021) were analyzed. Two-sample MR was conducted using inverse-variance weighted (IVW) as the primary method, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses to assess causal effects of genetically proxied lifestyle and socio-environmental factors on IBD and AD. Cross-disease transcriptomic analyses were performed to identify shared pathways.

Results: Parallel increases in IBD and AD burden were observed, with pronounced sociodemographic disparities and a steep rise in AD in aging, high-sociodemographic index (SDI) populations. Higher genetically proxied educational attainment was associated with reduced risk of IBD (odds ratio [OR] = 0.87, 95% confidence interval [CI] = 0.80–0.94) and AD (OR = 0.82, 95% CI = 0.74–0.91). Higher coffee consumption increased IBD (OR = 1.20, 95% CI = 1.09–1.33) and AD risk (OR = 1.19, 95% CI = 1.05–1.35). Higher beef intake had an inverse association with IBD (OR = 0.48, 95% CI = 0.27–0.88) and AD (OR = 0.0012, 95% CI = 0.0006–0.0025). Transcriptomic analyses demonstrated concordant dysregulation of inflammatory and immune pathways, including TNF/NF-κB signaling. Projections indicated a continued escalation of AD burden to 2050.

Conclusions: Convergent epidemiologic, causal, and molecular evidence indicates that IBD and AD share modifiable determinants along the gut–brain axis. These findings highlight opportunities for coordinated prevention strategies targeting chronic inflammatory disease trajectories.

Keywords

Alzheimer’s disease / genome-wide association studies / GBD / IBD / Mendelian randomization

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Liuxi Chu, Zhongpeng Dai, Sisi Wang, Qiang Li, Wenyuan Wang, Ping Wu, Xun Chen, Jiping Wei, Yuqing Li, Wenjie Hu, Chen Gao, Wenjia Wang, Quan Zhang, Zunyong Feng, Xiaokun Li, Zhouguang Wang. Convergence of Epidemiology and Modifiable Causal Risk Factors in Inflammatory Bowel Disease and Alzheimer’s Disease. BIO Integration, 2026, 7 (1) : 22 DOI:10.15212/bioi-2026-0023

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