College of Basic Medical Sciences, Changchun University of Traditional Medicine, Changchun, China.
College of Integrative Medicine, Changchun University of Traditional Medicine, Changchun, China.
Microbiol Spectr. 2024 Nov 5;12(11):e0149024. doi: 10.1128/spectrum.01490-24. Epub 2024 Oct 15.
Exploring the link between gut microbiota and chronic gastritis (CG), and assessing the potential mediating influence of blood metabolites. Using aggregated data from genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to explore the genetic links between gut microbiota (412 types) and CG (623,822 cases). Furthermore, we utilized a two-step MR approach to measure the extent to which blood metabolites (1,400 types) mediate the impact of gut microbiota on CG. Through MR, we identified that three genetically predicted gut microbiota increased the risk of CG: the ubiquinol-8 biosynthesis pathway (OR 1.149, 95%CI 1.022-1.291), from the Porphyromonadaceae family (OR 1.260, 95%CI 1.044-1.523), and from the Lachnospiraceae family (OR 1.125, 95%CI 1.010-1.253). Currently, there is no evidence to suggest that genetically predicted CG affects the risk of gut microbiota. Four blood metabolites mediated the proportionate changes in genetically predicted gut microbiota: levels of 4-hydroxyphenylacetate levels by 14.9% (95% CI -0.559%, 30.3%), palmitoleate (16:1n7) levels, and the phosphate to alanine ratio together mediated the same microbiota by 6.97% (95% CI -1.61%, 15.6%) and 7.91% (95% CI -1.67%, 17.5%), while the phosphate to alanine ratio and X-12839 levels together mediated the same microbiota by 8.48% (95% CI -2.87%, 19.8%) and 10.7% (95% CI 0.353%, 21.1%). In conclusion, our research has confirmed a causal link between gut microbiota, blood metabolites, and CG. Metabolites such as 4-hydroxyphenylacetate levels, palmitoleate (16:1n7) levels, the phosphate to alanine ratio, and X-12839 levels have relatively significant mediating roles between gut microbiota and CG. These metabolites may influence the occurrence and development of CG by regulating inflammatory responses, energy metabolism, and gut barrier function. However, the majority of the influence of gut microbiota on CG remains unclear, necessitating further research into other potential mediating risk factors. Clinically, it is crucial to focus on patients suffering from CG who exhibit dysbiosis of gut microbiota.IMPORTANCEThe results indicate that interactions between particular gut microbiota and blood metabolites may significantly contribute to the onset and progression of CG. These findings offer new insights and potential targets for early diagnosis, personalized treatment, and prevention of CG.
探讨肠道微生物群与慢性胃炎（CG）之间的联系，并评估血液代谢物的潜在中介影响。我们使用全基因组关联研究（GWAS）的汇总数据，进行了两样本孟德尔随机化（MR）分析，以探索肠道微生物群（412 种类型）与 CG（623822 例）之间的遗传联系。此外，我们利用两步 MR 方法来衡量血液代谢物（1400 种类型）在多大程度上介导肠道微生物群对 CG 的影响。通过 MR，我们确定了三种遗传预测的肠道微生物群会增加 CG 的风险：泛醌-8 生物合成途径（OR 1.149，95%CI 1.022-1.291）、卟啉单胞菌科（OR 1.260，95%CI 1.044-1.523）和lachnospiraceae 科（OR 1.125，95%CI 1.010-1.253）。目前，没有证据表明遗传预测的 CG 会影响肠道微生物群的风险。四种血液代谢物介导了遗传预测的肠道微生物群的比例变化：4-羟基苯乙酸水平变化 14.9%（95%CI-0.559%，30.3%），棕榈油酸（16:1n7）水平和磷酸丙氨酸比共同介导相同的微生物群 6.97%（95%CI-1.61%，15.6%）和 7.91%（95%CI-1.67%，17.5%），而磷酸丙氨酸比和 X-12839 水平共同介导相同的微生物群 8.48%（95%CI-2.87%，19.8%）和 10.7%（95%CI 0.353%，21.1%）。总之，我们的研究证实了肠道微生物群、血液代谢物和 CG 之间存在因果关系。4-羟基苯乙酸水平、棕榈油酸（16:1n7）水平、磷酸丙氨酸比和 X-12839 水平等代谢物在肠道微生物群与 CG 之间具有相对显著的中介作用。这些代谢物可能通过调节炎症反应、能量代谢和肠道屏障功能来影响 CG 的发生和发展。然而，肠道微生物群对 CG 的大部分影响仍不清楚，需要进一步研究其他潜在的中介风险因素。临床上，需要关注患有 CG 的患者，这些患者的肠道微生物群存在失调。重要的是，特定的肠道微生物群和血液代谢物之间的相互作用可能会显著影响 CG 的发生和发展。这些发现为 CG 的早期诊断、个体化治疗和预防提供了新的见解和潜在的靶点。
