Research Paper|Volume 16, Issue 4|pp 3596—3611

Causal relationship between gut microbiota and risk of esophageal cancer: evidence from Mendelian randomization study

Kui Wang^1,², Jiawei Wang³, Yuhua Chen⁵, Huan Long^1,², Wei Pan⁶, Yunfei Liu⁷, Ming-Yi Xu⁴, Qiang Guo¹

¹Department of Gastroenterology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan, China
²Medical School, Kunming University of Science and Technology, Kunming 650500, Yunnan Province, China
³Department of Critical Care Medicine, Jieyang Third People’s Hospital, Jieyang 515500, Guangdong Province, China
⁴Department of Gastroenterology, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai 310115, China
⁵The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
⁶Cardiology Department, Geriatrics Department, Foshan Women and Children Hospital, Foshan 528000, Guangdong, China
⁷University Munich, Munich D-81377, Germany

* Equal contribution

Received: October 19, 2023Accepted: January 11, 2024Published: February 15, 2024

https://doi.org/10.18632/aging.205547

Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The causative implications remain ambiguous. Consequently, this study aims to evaluate the putative causal relationship between gut microbiota and Esophageal cancer (EC).

Methods: The genome-wide association study (GWAS) pertaining to the microbiome, derived from the MiBioGen consortium-which consolidates 18,340 samples across 24 population-based cohorts-was utilized as the exposure dataset. Employing the GWAS summary statistics specific to EC patients sourced from the GWAS Catalog and leveraging the two-sample Mendelian randomization (MR) methodology, the principal analytical method applied was the inverse variance weighted (IVW) technique. Cochran’s Q statistic was utilized to discern heterogeneity inherent in the data set. Subsequently, a reverse MR analysis was executed.

Results: Findings derived from the IVW technique elucidated that the Family Porphyromonadaceae (P = 0.048) and Genus Candidatus Soleaferrea (P = 0.048) function as deterrents against EC development. In contrast, the Genus Catenibacterium (P = 0.044), Genus Eubacterium coprostanoligenes group (P = 0.038), Genus Marvinbryantia (P = 0.049), Genus Ruminococcaceae UCG010 (P = 0.034), Genus Ruminococcus1 (P = 0.047), and Genus Sutterella (P = 0.012) emerged as prospective risk contributors for EC. To assess reverse causal effect, we used EC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between EC and seven different types of gut microbiota. The robustness of the MR findings was substantiated through comprehensive heterogeneity and pleiotropy evaluations.

Conclusions: This research identified certain microbial taxa as either protective or detrimental elements for EC, potentially offering valuable biomarkers for asymptomatic diagnosis and prospective therapeutic interventions for EC.