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Genetic Insight Into Dissecting the FODMAP Diet Frame and Liver Cancer: The Mediation Role of Efferocytosis and Trogocytosis.

作者信息

Ma Xiang, Lei Kai, Liu Zuojin

机构信息

Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical University Chongqing China.

出版信息

Food Sci Nutr. 2025 Aug 29;13(9):e70883. doi: 10.1002/fsn3.70883. eCollection 2025 Sep.


DOI:10.1002/fsn3.70883
PMID:40895144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12395182/
Abstract

The etiology of liver cancer remains poorly understood, particularly regarding its potential association with dietary patterns rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP). This study investigated the genetic relationships between FODMAP-related dietary intake and liver cancer risk and further assessed whether proteins involved in efferocytosis and trogocytosis mediate these associations. This study applied two-sample Mendelian randomization (MR) and mediation MR analyses to examine the links among FODMAP-related dietary factors, trogocytosis, efferocytosis, and liver cancer. Summary statistics were obtained from MVP-GWAS for liver cancer, deCODE for trogocytosis and efferocytosis, and the UK Biobank for FODMAP dietary traits. A two-step mediation MR analysis was then performed to determine whether the pathways of efferocytosis and trogocytosis mediated the genetic associations between FODMAP foods and liver cancer, with mediation proportions calculated accordingly. MR analyses revealed that higher consumption of cheese (OR = 0.548, 95% CI = 0.404-0.743), fresh fruit (OR = 0.375, 95% CI = 0.194-0.727), cereal (OR = 0.575, 95% CI = 0.386-0.857), and dried fruit (OR = 0.539, 95% CI = 0.340-0.853) was significantly associated with a reduced risk of liver cancer. Protein-level analyses identified four trogocytosis- and efferocytosis-related proteins, TGFB3, EPOR, ELANE, and C3, that may mediate these dietary effects on liver cancer susceptibility. Mediation MR indicated that cheese intake influenced liver cancer risk indirectly by modulating TGFB3, EPOR, ELANE, and C3 expression, accounting for 8.8%, 25%, 1.8%, and 12.7% of the total effect, respectively. Sensitivity analyses for heterogeneity and pleiotropy supported the robustness of these findings. This study uncovers a potential molecular mechanism by which FODMAP-related dietary patterns may modulate liver cancer risk through the TGFB3/EPOR/ELANE/C3 signaling axis. These results provide genetic evidence and mechanistic insights supporting the role of FODMAP-oriented dietary strategies in liver cancer prevention, offering a theoretical basis for future public health interventions.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/dbfaf0eb80fc/FSN3-13-e70883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/15370114472e/FSN3-13-e70883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/6c5973022fc2/FSN3-13-e70883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/a60d1c2d7a23/FSN3-13-e70883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/5cd68a12553f/FSN3-13-e70883-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/dbfaf0eb80fc/FSN3-13-e70883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/15370114472e/FSN3-13-e70883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/6c5973022fc2/FSN3-13-e70883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/a60d1c2d7a23/FSN3-13-e70883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/5cd68a12553f/FSN3-13-e70883-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d8/12395182/dbfaf0eb80fc/FSN3-13-e70883-g001.jpg

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本文引用的文献

[1]
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Science. 2024-7-19

[2]
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Cancers (Basel). 2024-3-2

[3]
Gut microbiota and metabolite interface-mediated hepatic inflammation.

Immunometabolism (Cobham). 2024-1-25

[4]
The effects of whole grain cereals on tryptophan metabolism and intestinal barrier function: underlying factors of health impact.

Proc Nutr Soc. 2024-2

[5]
Causal relationship between endometriosis with infertility and ankylosing spondylitis.

Sci Rep. 2023-8-17

[6]
Therapeutic modulation of the liver immune microenvironment.

Hepatology. 2023-11-1

[7]
Inhibiting efferocytosis reverses macrophage-mediated immunosuppression in the leukemia microenvironment.

Front Immunol. 2023

[8]
Management of Hepatocellular Carcinoma: A Review.

JAMA Surg. 2023-4-1

[9]
Upregulated antimicrobial immune response mediated by neutrophils in the development from allergic rhinitis to asthma.

Front Immunol. 2022

[10]
Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.

Cell Prolif. 2023-1

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