Enteropathway: the metabolic pathway database for the human gut microbiota

Abstract

The human gut microbiota produces diverse, extensive metabolites that have the potential to affect host physiology. Despite significant efforts to identify metabolic pathways for producing these microbial metabolites, a comprehensive metabolic pathway database for the human gut microbiota is still lacking. Here, we present Enteropathway, a metabolic pathway database that integrates 3269 compounds, 3677 reactions, and 876 modules that were obtained from 1012 manually curated scientific literature. Notably, 698 modules of these modules are new entries and cannot be found in any other databases. The database is accessible from a web application (https://enteropathway.org) that offers a metabolic diagram for graphical visualization of metabolic pathways, a customization interface, and an enrichment analysis feature for highlighting enriched modules on the metabolic diagram. Overall, Enteropathway is a comprehensive reference database that can complement widely used databases, and a tool for visual and statistical analysis in human gut microbiota studies and was designed to help researchers pinpoint new insights into the complex interplay between microbiota and host metabolism.

Keywords: human gut microbiota; microbial metabolic pathway database; visualization tool.

Figure 1

The overview of the database. The database (DB) was developed from the scientific literature by manual curation. This DB is composed of compounds, reactions, and modules. Each compound, reaction, and module is assigned an entry ID and a name. The reaction represents the chemical transformation for producing/degrading compounds. The arrow refers to the direction of the reaction. The module is generally defined as multiple reaction processes. The triangle represents one reaction in the module.

Figure 2

The user interface of the web application. The web application displays the metabolic pathway (a), search engine (b), and customization interface (c) at the following link: https://enteropathway.org/#/diagram. (a) Compounds are represented by circles, and reactions are represented by arrows. Each module is displayed as a series of connected circles and arrows, with its title in a box. These elements are arranged based on the module category within the metabolic pathway. (b) The search engine allows users to explore entry IDs by inputting their names as keywords and highlighting them on the metabolic pathway. (c) The customization interface enables users to characterize reactions, compounds, and modules on the metabolic pathway, as defined by their input data, by clicking the submit button. Zooming in and zooming out functions are available through the plus and minus buttons on the left side. The middle button between the plus and minus buttons on the left side can reset the initial zoom. The button under the minus button on the left side can restore the original metabolic pathway.

Figure 3

The metabolic pathway after customization of the metagenomic and metabolomic data. The pathway displays the enrichment of centenarian-specific compounds (circles), reactions (arrows), and modules (boxes). The shared link is https://enteropathway.org/#/diagram/zuRUQPb3tV_00tnw3IHfD5X2iWDxtrE00qD0duzsQCR-HPA6dWlsncKavduC9-RfhralrDnmy42q6W2W4EV37Y88XwqSD9FlyTgGPInmqyeKJZMhgusoenMLEBNZtRdxZ8UzcTtm8MGZHOUujn9Zj2tz0a7wa55PnjBli-k6P9CuaOBgZ97TiDTIt9oOGN6HZunxU9uYWBwydWo31aEKLkjSAEM0pxJpsbNWLqc-VA6OAck0lE3PbPXkvA-4KrDI. Centenarian-specific reactions, compounds, and modules are identified by the Wilcoxon rank-sum test or the hypergeometric test. The significance of differences (Q < 0.1) is represented by varying sizes and opacities of the circles, arrows, and boxes, indicating whether they are enriched, depleted, or non-significant in Centenarians.