| Title: | Dietary modulation of metabo-proteomic reprogramming by the EAT-lancet diet attenuates colorectal cancer risk |
| Journal: | Clinical Nutrition |
| Published: | 23 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42400994/ |
| DOI: | https://doi.org/10.1016/j.clnu.2026.106716 |
Publication 20563
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Abstract
BACKGROUND AND AIMS: The EAT-Lancet diet was developed to support both human health and environmental sustainability and has been linked to multiple chronic diseases. However, its associations with metabolic profiles and circulating proteins in colorectal cancer (CRC) have not been comprehensively evaluated. This study aimed to investigate the association between adherence to the EAT-Lancet diet and CRC risk and to explore potential metabolic, inflammatory, and proteomic pathways that may mediate this relationship.</p>
METHODS: We included 106,944 UK Biobank participants who completed at least two 24-h dietary recalls. Cox regression models were used to assess associations between adherence to the EAT-Lancet diet and CRC risk. Mediation analyses evaluated the potential mediating roles of body mass index, inflammation, metabolites, and circulating proteins, while enrichment and single-cell analyses explored potential underlying mechanisms.</p>
RESULTS: During a median follow-up of 13.54 years, 1591 CRC cases were recorded. Higher adherence to the EAT-Lancet diet was associated with a 12.2%-28.9% lower risk of CRC, with the strongest effects observed in individuals with medium genetic risk. These associations remained consistent across sensitivity and stratified analyses, and dose-response relationships were detected. The potential protective effects of the EAT-Lancet diet on CRC risk were comparable to those observed for the Mediterranean diet. Nine metabolites and nine proteins were significantly associated with all EAT-Lancet indices. Mediation analyses suggested that high body mass index (9.0%-18.0%), protein score (29.2%), and low-grade inflammation (INFLA score, 4.0%) partially mediated the relationship between dietary adherence and CRC risk. Circulating protein GGT1 was negatively associated with the diet, with lower levels linked to reduced CRC risk. Single-cell analysis showed GGT1 enrichment in immune and epithelial cells within CRC tumors.</p>
CONCLUSION: Our findings suggest that greater adherence to the EAT-Lancet diet is associated with lower CRC risk and favorable metabolic and protein profiles, supporting its potential as a sustainable and economically viable dietary strategy for CRC prevention.</p>
STATEMENT OF SIGNIFICANCE: This study is the first to comprehensively characterize the metabolic and proteomic signatures associated with adherence to the EAT-Lancet diet and to explore their potential mediating roles in colorectal cancer (CRC) risk. By integrating multi-omics analyses with dietary assessments, we identified novel molecular pathways-particularly involving GGT1 and immune-inflammatory signaling-through which the EAT-Lancet diet may influence CRC development, providing mechanistic insights that extend beyond previous epidemiologic findings.</p>
8 Authors
- Jingyu Ye
- Jianhui Zhao
- Hao Wu
- Haosen Ji
- Siyun Zhou
- Evropi Theodoratou
- Konstantinos K Tsilidis
- Xue Li
Enabling scientific discoveries that improve human health