Gastroenterology · Endocrinology · 2 h ago
Multi-omics study identifies MASLD risk signatures and serum citramalic acid
A population-based cohort study of 1,694 participants assessed multi-omics markers and eight-year MASLD trajectories. Serum citramalic acid ranked highly among features associated with disease severity, while risk scores and subtypes showed associations with MASLD persistence and type 2 diabetes risk; key findings were replicated in an external cohort.
- Cohort included 1,694 participants with eight-year follow-up.
- Serum citramalic acid ranked highly among severity-associated features.
- Multi-omics risk scores were more strongly associated with persistent MASLD.
- Findings need clinical validation before use in risk stratification.
Researchers analyzed 1,694 participants in the Guangzhou Nutrition and Health Study, profiling gut metagenomics and targeted fecal and serum metabolomics. MASLD severity was assessed using MRI-derived liver steatosis, and repeated ultrasound examinations were used to characterize eight-year trajectories. The team also tested citramalic acid administration in high-fat-diet-fed mice.
The analysis identified nine microbial species, 13 fecal metabolites and 13 serum metabolites associated with MASLD severity; serum citramalic acid was the top-ranked feature. Per-standard-deviation increases in microbial-, fecal- and serum-metabolite risk scores were associated with MASLD incidence (hazard ratios 1.04, 1.18 and 1.21, respectively) and more strongly with persistent MASLD (odds ratios 1.27, 1.62 and 2.23). Three multi-omics subtypes showed worsening metabolic dysfunction across groups. The highest-risk subtype had greater odds of type 2 diabetes (OR 2.70; 95% CI 1.61–4.55). Key findings were replicated in an external cohort.
The results suggest potential avenues for MASLD risk stratification, but the identified signatures are not established clinical tests. The mouse experiment found worsening metabolic dysfunction and steatosis after citramalic acid administration, but does not establish that citramalic acid causes disease progression in people. The study was supported by public and academic grants; authors reported no competing interests.
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BMC Medicine: Multi-omics signatures of 8-year trajectories and heterogeneity of metabolic dysfunction-associated steatotic liver disease reveal serum citramalic acid as a key contributor ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.