Role of blood metabolites in mediating the effect of gut microbiota on chronic gastritis

Abstract

ABSTRACT 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), Odoribacter from the Porphyromonadaceae family (OR 1.260, 95%CI 1.044–1.523), and Coprococcus 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.

Keywords

• Mendelian randomization analysis
• gut microbiota
• blood metabolites
• chronic gastritis
• mediating effect