Serum metabolomics associated with gut Akkermansia. (A) Distribution of serum metabolites into pathways, provided to facilitate comparison with (C). (B) Volcano plot showing the strength and significance of the association between serum metabolite levels (outcome variable) and abundance of gut Akkermansia (predictor) in the nearest prior stool sample. For each metabolite, a separate mixed effect regression was created, adjusting for sex, use of parenteral nutrition, serum sample day, and patient number (random effect). The regression coefficient for Akkermansia was considered its effect size (x-axis), and the corresponding P value was corrected for multiple testing to derive the q value (y-axis). Select metabolites of interest in this work are labeled. The horizontal lines represent q = .05 and q = .1, above which the metabolites are statistically significant according to the corresponding threshold. (C) Distribution of metabolites with q < .1 in (B) into pathways. (D) Overrepresentation analysis using subpathways. Metabolites with q < .05 in (B) were considered for overrepresentation of their subpathways using a hypergeometric test with a corrected P value threshold of .05. Each central node represents an overrepresented subpathway, and the peripheral nodes connected to the central node represent the metabolites within that subpathway that are significant in (B). The number of these metabolites in each overrepresented subpathway is proportional to the size of the central node. The complete list of metabolites is provided in supplemental Data 2.