Skip to main content

ORIGINAL RESEARCH article

Front. Genet.
Sec. Nutritional Genomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1406230

Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study

Provisionally accepted
Tao Su Tao Su 1,2*Xiang Peng Xiang Peng 2Ying Gan Ying Gan 3Hongzhen Wu Hongzhen Wu 2Shulin Ma Shulin Ma 3Min Zhi Min Zhi 2Yi Lu Yi Lu 3Shi-xue Dai Shi-xue Dai 4Jiayin Yao Jiayin Yao 2
  • 1 Sun Yat-sen University, Guangzhou, China
  • 2 The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • 3 Department of Anesthesiology, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China, Guangzhou, China
  • 4 Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background: Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations.Objective: We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota.Methods: Independent genetic instruments linked with iron status were selected using a genome-wide threshold of P = 5 × 10 -6 from corresponding genome-wide association studies.Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia.Results: Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer.Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases.This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.

    Keywords: iron status, Gastrointestinal Diseases, Gut Microbiota, Mendelian randomization, liver cancer

    Received: 24 Mar 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Su, Peng, Gan, Wu, Ma, Zhi, Lu, Dai and Yao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tao Su, Sun Yat-sen University, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.