What question did this study set out to answer?

The study investigates how a dietary pattern supportive of gut microbiota influences the risk of MASLD and identifies metabolomic profiles involved in this relationship.

March 7, 2026Open Access

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

Key Points

The study investigates how a dietary pattern supportive of gut microbiota influences the risk of MASLD and identifies metabolomic profiles involved in this relationship.
Analyzed dietary and metabolomic data from 100,953 UK Biobank participants.
Calculated the Dietary Index for Gut Microbiota (DI-GM) based on 14 food components.
Conducted metabolomic profiling using NMR spectroscopy.
Employed LASSO regression for metabolic signature derivation.
Used Cox proportional hazards models to estimate hazard ratios for MASLD.
Each one-point increase in DI-GM correlated with a 15% reduction in MASLD risk.
Participants with a high DI-GM (≥ 7) had a hazard ratio of 0.68 for MASLD compared to those with a low DI-GM (≤ 4).
The metabolomic analysis identified a signature of 92 metabolites associated with DI-GM.
This metabolomic signature was linked to a 26% reduction in MASLD risk per standard deviation increase.
Mediation analysis indicated that the metabolic signature explained 34.2% of the association between DI-GM and MASLD risk.

Abstract

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. 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. 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. 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.

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Cite This Study

Li et al. (Thu,) studied this question.

synapsesocial.com/papers/69abc1535af8044f7a4e9ebd https://doi.org/https://doi.org/10.1186/s12937-026-01297-8

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