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Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 38% of adults worldwide. While diet influences MASLD development through multiple pathways, the role of gut microbiota-targeted dietary patterns remains unclear. We aimed to investigate the association between Dietary Index for Gut Microbiota (DI-GM) and incident MASLD risk, and to identify metabolomic signatures that may mediate this relationship.</p> Methods <p>We analyzed data from 100,953 UK Biobank participants with detailed dietary and metabolomic information. The DI-GM was calculated based on 14 food components with established effects on gut microbiota. Plasma metabolomic profiling was performed using NMR spectroscopy. A metabolic signature was derived through LASSO regression with cross-validation. Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MASLD.</p> Results <p>During a median follow-up of 13.46 years, 1,221 cases of MASLD were documented. Each one-point increase in DI-GM was associated with a 15% reduction in MASLD risk (HR: 0.85, 95% CI: 0.80–0.90). Participants in the highest DI-GM (≥ 7) had a HR of 0.68 (95% CI: 0.58–0.80) compared to the lowest (≤ 4). The metabolomic analysis identified a signature of 92 metabolites strongly correlated with DI-GM (<i>r</i> = 0.30, <i>P</i> &lt; 0.001). This signature was associated with a 26% reduction in MASLD risk per standard deviation increase (HR: 0.74, 95% CI: 0.69–0.79). Mediation analysis revealed that the metabolic signature explained 34.2% (95% CI: 19.3%–60.6%) of the association between DI-GM and MASLD risk.</p> Conclusions <p>Higher adherence to a gut microbiota supportive dietary pattern is associated with reduced risk of MASLD. The association is partially mediated through favorable alterations in metabolism. These findings support the implementation of gut microbiota-focused dietary strategies for chronic liver disease prevention.</p>

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Gut microbiota supportive dietary pattern associated with reduced MASLD risk mediated by metabolomic profiles: a prospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月5日

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  • Dong-Run Li,
  • Ke-Ru Li,
  • Ying Wang,
  • Jia-Qi Zheng,
  • Wen-Rui Zheng,
  • Bang-Quan Liu,
  • Jia-Cheng Liu,
  • Rui-Han Bao,
  • Ting-Ting Gong,
  • Qiu-Ju Sheng,
  • Shan-Yan Gao,
  • Qi-Jun Wu

摘要

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 38% of adults worldwide. While diet influences MASLD development through multiple pathways, the role of gut microbiota-targeted dietary patterns remains unclear. We aimed to investigate the association between Dietary Index for Gut Microbiota (DI-GM) and incident MASLD risk, and to identify metabolomic signatures that may mediate this relationship.

Methods

We analyzed data from 100,953 UK Biobank participants with detailed dietary and metabolomic information. The DI-GM was calculated based on 14 food components with established effects on gut microbiota. Plasma metabolomic profiling was performed using NMR spectroscopy. A metabolic signature was derived through LASSO regression with cross-validation. Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MASLD.

Results

During a median follow-up of 13.46 years, 1,221 cases of MASLD were documented. Each one-point increase in DI-GM was associated with a 15% reduction in MASLD risk (HR: 0.85, 95% CI: 0.80–0.90). Participants in the highest DI-GM (≥ 7) had a HR of 0.68 (95% CI: 0.58–0.80) compared to the lowest (≤ 4). The metabolomic analysis identified a signature of 92 metabolites strongly correlated with DI-GM (r = 0.30, P < 0.001). This signature was associated with a 26% reduction in MASLD risk per standard deviation increase (HR: 0.74, 95% CI: 0.69–0.79). Mediation analysis revealed that the metabolic signature explained 34.2% (95% CI: 19.3%–60.6%) of the association between DI-GM and MASLD risk.

Conclusions

Higher adherence to a gut microbiota supportive dietary pattern is associated with reduced risk of MASLD. The association is partially mediated through favorable alterations in metabolism. These findings support the implementation of gut microbiota-focused dietary strategies for chronic liver disease prevention.