Su Tao, Peng Xiang, Gan Ying, Wu Hongzhen, Ma Shulin, Zhi Min, Lu Yi, Dai Shixue, Yao Jiayin
Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Front Genet. 2024 Aug 7;15:1406230. doi: 10.3389/fgene.2024.1406230. eCollection 2024.
Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations.
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.
Independent genetic instruments linked with iron status were selected using a genome-wide threshold of = 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.
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.
铁状态与胃肠道疾病和肠道微生物群有关，然而，混杂因素可能会影响这些关联。
我们进行了孟德尔随机化（MR）研究，以调查铁状态，包括血铁含量、内脏铁含量和缺铁性贫血与24种胃肠道疾病发病率及肠道微生物群变化之间的关联。
使用来自相应全基因组关联研究的全基因组阈值=5×10-6选择与铁状态相关的独立遗传工具。与胃肠道疾病和肠道微生物群相关的遗传关联来自英国生物银行、芬兰基因研究和其他联盟。
遗传预测的铁和铁蛋白水平较高与肝癌风险较高相关。转铁蛋白饱和度较高与乳糜泻风险降低相关，但与非酒精性脂肪性肝病（NAFLD）和肝癌风险较高相关。脾脏铁含量较高与胰腺癌风险较低相关。此外，肝脏铁含量较高与NAFLD和肝癌风险较高相关。然而，在考虑遗传预测的香烟和酒精使用情况后，某些关联失去了统计学意义。然后，较高水平的铁和铁蛋白分别与11种肠道微生物群丰度相关。在一项二次分析中，较高的铁水平与较低的憩室病风险相关，较高的铁蛋白水平与较高的肝癌风险相关。较高的转铁蛋白饱和度被证明会增加NAFLD、酒精性肝病和肝癌的风险，但会降低食管癌的风险。MR分析显示铁状态、肠道微生物群和胃肠道疾病之间没有中介关系。
本研究提供的证据表明铁状态与胃肠道疾病和肠道微生物群，尤其是肝脏疾病之间可能存在因果关联。
