ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1607476
This article is part of the Research TopicInsights in Host Genetics and Microbial Interaction of Gastrointestinal DiseasesView all 5 articles
The host genes influencing Clostridioides difficile infection and the potential role of intestinal Lactobacillus acidophilus: a Mendelian randomization and animal model study
Provisionally accepted
Yuxin Sun1,2
Wenzhen Zhou1,2
Senlin Ma1,2Qiuxin Lu1,2Yinuo Yuan1Yanchao Zheng1,2Yifan Yang1,2Kangshuai Zhou1,2Qingjiang Chen1,2Gonghao Sun1,2Zhaoming Shang1,2Junwei Qian1,2Xiaofei Jiang1,2*
Mingquan Chen1,2*- 1Fudan University, Shanghai, China
- 2Huashan Hospital, Fudan University, Shanghai, Shanghai Municipality, China
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Clostridioides difficile infection (CDI) poses a significant clinical burden due to its high recurrence rate and life-threatening complications. While gut dysbiosis is central to CDI pathogenesis, mechanisms underlying microbiota-mediated host defense remain underexplored. This study integrated summary-data-based Mendelian randomization (SMR) of cis-expression quantitative trait loci (cis-eQTLs) from blood, transverse colon, and sigmoid colon tissues with CDI genome-wide association study (GWAS) data to identify host genes influencing CDI susceptibility. Bayesian co-localization was employed to validate relationships. SMR analysis identified 14 genes associated with CDI risk, primarily clustered in the major histocompatibility complex (MHC) region. Notably, THOC5 exhibited robust associations (PSMR < 0.05 in all tissues) and co-localization evidence (posterior probability = 82.6%). Then a germ-free (GF) mice model colonized with Lactobacillus acidophilus (LA) was used to investigate LA-mediated regulation of host Thoc5 expression. In GF mice, LA colonization significantly upregulated colonic Thoc5 expression in two independent experiments (fold change = 5.19/5.00, P = 0.034/0.031). Subsequent immunofluorescence experiments revealed that LA colonisation enhanced macrophage activation in the colonic tissue. These findings reveal key host genes, particularly THOC5, that influence susceptibility to CDI, providing new targets for future prevention and treatment research. Additionally, the study suggests a potential mechanism by which host intestinal LA protects against CDI, highlighting the interaction between probiotics and host transcriptional networks in CDI resistance. These insights offer valuable directions for further investigation.
Keywords: Clostridioides difficile infection, Gut probiotics, Lactobacillus acidophilus, THOC5 gene, Mendelian randomization No. 12, Urumqi Middle Road, Jing'an District, Shanghai
Received: 08 Apr 2025; Accepted: 20 Jun 2025.
Copyright: © 2025 Sun, Zhou, Ma, Lu, Yuan, Zheng, Yang, Zhou, Chen, Sun, Shang, Qian, Jiang and Chen. 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:
Xiaofei Jiang, Fudan University, Shanghai, China
Mingquan Chen, Fudan University, Shanghai, China
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