Assessment of causal associations among gut microbiota, metabolites, and celiac disease: a bidirectional Mendelian randomization study

Abstract

BackgroundA growing number of studies have implicated that gut microbial abundance and metabolite concentration alterations are associated with celiac disease (CD). However, the causal relationship underlying these associations is unclear. Here, we used Mendelian randomization (MR) to reveal the causal effect of gut microbiota and metabolites on CD.MethodsGenome-wide association study (GWAS) summary-level data for gut microbiota, metabolites, and CD were extracted from published GWASs. Causal bacterial taxa and metabolites for CD were determined by two-sample MR analyses. The robustness of the results was assessed with sensitivity analyses. Finally, reverse causality was investigated with a reverse MR analysis.ResultsGenetically, increased genus Bifidobacterium was potentially associated with higher CD risk (odds ratio [OR] = 1.447, 95% confidence interval [CI]: 1.054–1.988, p = 0.022) while phylum Lentisphaerae (OR = 0.798, 95% CI: 0.648–0.983, p = 0.034) and genus Coprobacter (OR = 0.683, 95% CI: 0.531–0.880, p = 0.003) were related to lower CD risk. Moreover, there were suggestive associations between CD and the following seven metabolites: 1-oleoylglycerophosphoethanolamine, 1-palmitoylglycerophosphoethanolamine, 1,6-anhydroglucose, phenylacetylglutamine, tryptophan betaine, 10-undecenoate, and tyrosine. Sensitivity analyses deemed the results reliable without pleiotropy.ConclusionWe investigated the causal relationships between gut microbiota, metabolites, and CD with two-sample MR. Our findings suggest several novel potential therapeutic targets for CD treatment. Further understanding of the underlying mechanism may provide insights into CD pathogenesis.

Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals

“…Finally, concerning the genera that correlated positively with red meat consumption, we found genera related to inflammatory bowel disease, such as Faecalicoccus and Clostridium sensu stricto [ 62 , 63 ]; Anaerofustis , which is related to ulcerative colitis but also to greater longevity [ 63 , 83 ]; and other genera that are more related to a good state of health, such as Phascolarctobacterium and Subdoligranulum [ 69 , 84 ]. The genera found to be inversely correlated with red meat consumption were mostly related to anti-inflammatory function, protection against some types of cancer, or low risk of celiac disease [ 82 , 85 , 86 ].…”

Mendelian randomization study revealed a gut microbiota-neuromuscular junction axis in myasthenia gravis

“…Meanwhile, MR analyses demonstrated different effects of the host-genetic driven increase in Lentisphaerae on the risk of different diseases. For example, Ning et al revealed suggestive causal effects of increased abundance of phylum Lentisphaerae, class Lentisphaeria, and order Victivallales on protective effects of Parkinson's disease 23 ; while a greater abundance of Lentisphaerae was identified to be significantly associated with lower celiac disease risk 24 . In our study, an increased abundance of the three taxa was causally linked to an increased risk of MG, indicating their detrimental effects on MG.…”

Mendelian randomisation analysis for intestinal disease: achievement and future

“…[77][78][79] Genetically predicted genus Bifidobacterium was related to an increased risk of coeliac disease, while phylum Lentisphaerae and genus Coprobacter were associated with a decreased risk. 84 However, the small sample size of GWAS of intestinal microbiota in current MR studies limits the selection of instrument variables. 83 The population samples of intestinal flora that Li et al 83 used are relatively small which is attributed to the potential insufficient statistical efficacy.…”