Microbiome of organs mapped in 3D

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Researchers from the University of San Diego (UC San Diego; CA, USA) have developed the first tool to map microbiome and metabolomic data onto whole organs, giving a 3D spatial visualization. This could aid clinicians and researchers in understanding the effect of chemicals, such as microbial metabolites or drug compounds, on a diseased organ and its microbial community.

The microbial make-up within organs is determined by the environment and anatomy of the organ in question; however, our understanding of this is currently poor. Lead author, Pieter Dorrestein (UC San Diego) commented: “Our understanding of the spatial variation of the chemical and microbial make-up of a human organ remains limited. This is in part due to the size and variability of human organs, and the sheer amount of data we get from metabolomics and genomics studies.”

To try and address this gap, the team developed an open-source workflow, which could map metabolomics and microbiome data onto a 3D organ reconstruction produced from radiological imaging. The findings, published recently in Cell Host & Microbe, allowed the team to observe spatial variations and interactions that have not previously been uncovered.

To create the model, the researchers utilized a lung from a cystic fibrosis patient, and sectioned this – taking samples for the presence of bacteria, virulence factors, metabolites and any medications. The 3D organ reconstruction was produced from CT scans of a human lung, and an extension to Google Chrome, termed ‘ili’, was modified by the team to allow a visualization of the sample data across the entire organ.

Neha Garg (now at Georgia Tech, GA, USA) stated: “The application enables the user to map data onto a 2D or 3D surface, so we modified the code to allow us to map the abundance data not only onto surfaces, but also within the model.”

With this new data, including open-source maps of 16,379 molecules and 56 microbes visualised in 3D, the researchers discovered region-specific metabolism of medications placed in the context of microbial distribution.

Garg explained: “We could see that one of the antibiotics administered to the patient prior to collecting the tissue did not penetrate the bottom of the lung – a phenomenon that has not been observed before. This correlated with a higher abundance of the cystic fibrosis-associated pathogen Achromobacter. Thus, different drugs may differentially penetrate the lung, limiting exposure to effective dosage. Our tool allows researchers and clinicians to visualize this significant clinical concern within a human organ for the first time. This has implications for treatment of cystic fibrosis and other diseases.”

The team hopes this work will improve targeted drug delivery for antibiotics, and their data can serve as a resource for both researchers and clinicians.

Dorrestein concluded: “As future studies unravel more about the microbiome and metabolome, their spatial visualization will provide a means to infer their biological significance. Furthermore, the methodology developed can be extended to any human organ – notably those with tumors, which are known to be associated with their own unique microbiomes.”

Sources: Garg N, Wang M, Hyde E et al. Three-Dimensional Microbiome and Metabolome Cartography of a Diseased Human Lung. Cell Host Microb. doi:10.1016/j.chom.2017.10.001(2017) (Epub ahead of print); http://ucsdnews.ucsd.edu/pressrelease/the_microbial_anatomy_of_an_organ

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