| Title: | Dietary index for gut microbiota and risk of incident gastroesophageal reflux disease: a prospective cohort analysis integrating plasma proteomics in the UK Biobank |
| Journal: | Frontiers in Nutrition |
| Published: | 7 Jul 2026 |
| DOI: | https://doi.org/10.3389/fnut.2026.1880631 |
| URL: | https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2026.1880631/pdf |
Publication 20386
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Abstract
Gastroesophageal reflux disease (GERD) is a common chronic digestive disorder, and diet is an important modifiable risk factor. The Dietary Index for Gut Microbiota (DI-GM) reflects dietary patterns considered favorable to the gut microbiota; however, the gut microbiome itself was not measured, and evidence on whether DI-GM is associated with GERD risk is limited. We aimed to evaluate the association between DI-GM and incident GERD and to explore potential intermediate pathways using mediation analysis and plasma proteomics. We included 133,915 UK Biobank participants free of GERD at baseline. DI-GM scores (range 0-14) were calculated from the Oxford WebQ 24-h dietary recall and grouped into four categories (0-3, 4, 5, ≥6). Incident GERD was identified from the UK Biobank first-occurrence records (ICD-10 K21). Cox proportional hazards regression was complemented by restricted cubic spline (RCS), subgroup, and Cox weighted quantile sum (WQS) analyses, counterfactual mediation analysis, integrated plasma proteomics (Olink Explore 3072), and a range of sensitivity analyses. During a median follow-up of 13.6 years, 12,271 incident GERD cases occurred. In the fully adjusted model, each 1-point increase in DI-GM was associated with an approximately 4% lower hazard of GERD [hazard ratio (HR) 0.956, 95% CI 0.947-0.965; P < 0.001], and the highest DI-GM group (≥6) had a lower hazard than the lowest (0-3) (HR 0.812, 95% CI 0.774-0.851; P for trend < 0.001). RCS analysis showed a modest inverse dose-response relationship that was most apparent at higher DI-GM scores, and WQS analysis indicated that the association was driven by a few key components rather than shared equally across the index. BMI (proportion mediated 21.43%) and phenotypic age acceleration (7.53%) both significantly mediated the association (both P < 0.001). Integrated proteomic analysis identified 13 shared proteins; the nine positively associated with DI-GM and inversely associated with GERD showed exploratory enrichment in neurodevelopment- and cell-adhesion-related processes. Higher DI-GM was associated with a lower incidence of medically attended GERD, with mediation analysis suggesting that BMI and biological aging may partly account for this association. Exploratory proteomic analyses identified shared protein correlates, including adiposity-related and, tentatively, neurodevelopment- and cell-adhesion-related proteins; these are hypothesis-generating and require confirmation. Because the gut microbiome was not measured, the diet-microbiota link remains inferential, and these findings should be interpreted as associations rather than established mechanisms.</p>
8 Authors
- Yingxuan Huang
- Xiaobo Liu
- Chanchan Lin
- Yingyi Li
- Apei Zhou
- Yisen Huang
- Yubin Wang
- Xiaoqiang Liu
1 Application
| Application ID | Title |
|---|---|
| 1099827 | Determinants and Prognostic Impact of Multimorbidity in Irritable Bowel Syndrome: A Comprehensive Analysis of Behavioural, Environmental, Socioeconomic and Genetic Factors |
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