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Predicting the potential deterioration of Barrett's esophagus based on gut microbiota: a Mendelian randomization analysis.
Li, Conghan; Shu, Panyin; Shi, Taiyu; Chen, Yuerong; Mei, Ping; Zhang, Yizhong; Wang, Yan; Du, Xinyan; Wang, Jianning; Zhang, Yixin; Liu, Bin; Sheng, Zhijin; Chan, Shixin; Dan, Zhangyong.
Afiliação
  • Li C; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Shu P; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, 610041, China.
  • Shi T; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Chen Y; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Mei P; Department of Radiology, Anqing Municipal Hospital, Anqing, Anhui Province, 246000, China.
  • Zhang Y; College of Anesthesia, Wannan Medical College, No. 22 Wenchang West Road, Yijiang District, Wuhu City, 241002, Anhui, China.
  • Wang Y; College of Life Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Du X; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Wang J; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Zhang Y; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Liu B; First Clinical Medical College (First Affiliated Hospital), Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  • Sheng Z; Department of Physical Education, College of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, China. shengzhijin@ahmu.edu.cn.
  • Chan S; Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230032, China. chanshixin@163.com.
  • Dan Z; Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. ahmudzy@163.com.
Mamm Genome ; 35(3): 399-413, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38886201
ABSTRACT
Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esôfago de Barrett / Neoplasias Esofágicas / Adenocarcinoma / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Análise da Randomização Mendeliana / Microbioma Gastrointestinal Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esôfago de Barrett / Neoplasias Esofágicas / Adenocarcinoma / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Análise da Randomização Mendeliana / Microbioma Gastrointestinal Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article