Dietary index for gut microbiota and risk of gastrointestinal cancer: a prospective gene-diet study

Abstract

Background: The dietary index for gut microbiota (DI-GM) is a newly proposed index that evaluates dietary intake patterns associated with gut microbial health. Limited studies have examined whether DI-GM influences gastrointestinal (GI) cancer risk. We aimed to investigate the association between DI-GM and GI cancer risk and evaluate its combined effect with genetic risk.

Methods: We included 178,148 UK Biobank participants who completed at least one 24-hour dietary recall. DI-GM was constructed from 13 dietary components known to influence gut microbial health and was divided into three groups. The GI cancer polygenic risk score was calculated from 205 significant single-nucleotide polymorphisms related to esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Cox proportional hazards models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the associations between DI-GM, genetic risk, and GI cancer.

Results: During a median follow-up of 13.47 years, 2,682 participants developed GI cancer. In fully adjusted models, higher DI-GM was associated with a lower GI cancer risk (HR for GI cancer: 0.83; 95% CI: 0.75-0.92; HR for EC: 0.62, 95% CI: 0.45-0.86; HR for GC: 0.99, 95% CI: 0.71-1.39; HR for CRC: 0.84, 95% CI: 0.75-0.95), compared with participants in the lowest DI-GM category. In joint analysis, individuals with higher DI-GM and lower genetic risk had lower GI cancer risk, with HRs (95% CI) of 0.28 (0.21, 0.36), 0.50 (0.42, 0.58) for low and intermediate genetic risk, respectively, compared with those with low DI-GM and high genetic risk. And a significant interaction between DI-GM and genetic risk was observed.

Conclusion: Higher DI-GM was associated with a lower risk of GI cancer including EC and CRC. These findings highlight the importance of considering a gut microbiota-friendly diet and genetic risk in GI cancer prevention.

Keywords: Dietary index for gut microbiota; Gastrointestinal cancer; Genetic risk.

Fig. 1

Associations of DI-GM with risk of gastrointestinal cancer. Low: DI-GM ≤ 4; moderate: 5 ≤ DI-GM ≤ 6; high: DI-GM ≥ 7. The models adjusted for age, sex, body mass index, total energy intake, annual household income, education level, Townsend deprivation index, smoking status, alcohol consumption, family history of cancer, and physical activity level. Abbreviations: CI, confidence interval; CRC, colorectal cancer; DI-GM: dietary index for gut microbiota; EC, esophageal cancer; GC, gastric cancer; GI: gastrointestinal; HR, hazard ratio

Fig. 2

Restricted cubic splines for DI-GM and risk of (A) gastrointestinal cancer, (B) esophageal cancer, (C) gastric cancer, and (D) colorectal cancer. The models adjusted for age, sex, body mass index, total energy intake, annual household income, education level, Townsend deprivation index, smoking status, alcohol consumption, family history of cancer, and physical activity level. Abbreviations: CI, confidence interval; DI-GM: dietary index for gut microbiota

Fig. 3

Restricted cubic splines for CPRS and risk of gastrointestinal cancer. The models adjusted for age, sex, body mass index, total energy intake, annual household income, education level, Townsend deprivation index, smoking status, alcohol consumption, family history of cancer, and physical activity level. Abbreviations: CI, confidence interval; CPRS, cancer polygenic risk score. Abbreviations: CI, confidence interval; HR, hazard ratio

Fig. 4

Joint effect of DI-GM and genetic risk on gastrointestinal cancer incidence. Low: DI-GM ≤ 4; moderate: 5 ≤ DI-GM ≤ 6; high: DI-GM ≥ 7. The models adjusted for age, sex, body mass index, energy intake, annual household income, education level, Townsend deprivation index, smoking status, alcohol consumption, family history of cancer, and physical activity level. Abbreviations: CI, confidence interval; CPRS, cancer polygenic risk score; HR, hazard ratio