Developing Signatures that Relate Fecal Microbiome Characteristics with Patient Phenotype
EMSL Project ID
48612
Abstract
The exploration of the human microbiome is currently an area of keen interest to NIH and biotech firms, and has been explored by many researchers using either NMR or MS metabolomics or 16S rDNA sequencing. To our knowledge, there are no current tools allowing the researchers to conveniently correlate these multiple data types for a holistic understanding of the microbiome. This project pairs EMSL resource data collection with PNNL SDI Tools in support of the EMSL Mission, “… to provide integrated experimental and computational resources for discovery and technological innovation in the environmental molecular sciences”, and the EMSL Biology Science Theme, “Understand the foundational biological principles for predictive biology. Translating molecular and metabolic information into an understanding of the functioning of biological networks…” To achieve a more holistic understanding of the fecal microbiome in a systems biology context, we propose: 1) to utilize EMSL Nuclear Magnetic Resonance (NMR) resources to collect metabolomics data on fecal extract samples, 2) to correlate this data with ASU 16S rDNA sequencing data, in order to determine biomarkers that are indicative of patient health status, 3) to use Mass Spectrometry (MS) resources to determine both MS-detected metabolomics and MS-detected bile acid composition in selected matched samples (matched for NMR and MS data collection), and 4) for matched samples, to integrate disparate data types using PNNL Signature Discovery Initiative (SDI) Tools. Understanding the complex relationships in mixed microbial communities and host-microbiome interactions directly addresses the EMSL Science Theme of Biological Interactions and Dynamics: “Developing a quantitative, systems-level understanding of the dynamic network of proteins and molecules that drive cell responses and how groups of different cells interact to give rise to functional cell communities.” We anticipate discovering novel metabolite biomarkers and expanding the mechanistic understanding of the microbe-microbe and host-microbe interactions, which will have broad application to the field of microbial metabolomics. We will then integrate and interpret the results using mathematical modeling of the structure and function of the intestinal community. Combining the EMSL-generated “omics” data with phylogenetic analyses in the parent grant will provide a significant enhancement in understanding the systems biology.” A functional phylogeny of key microbial players will be reconstructed based on metabolomics data, enabling us to bridge the gap between phylogenetics of gut microbiome and its metabolic function in the context of surgical weight loss. The proposed work is expected to have wide application to those investigating complex biological communities, and the resultant methodologies to determine complex bio-signatures will be a platform for developing proposals of interest to NIH, DOE-BER, EPA and other funding streams, in accordance with the BER Mission, “…advances world-class biological and environmental research programs and scientific user facilities to support DOE’s energy, environment, and basic research missions… to understand how genomic information is translated to functional capabilities, enabling more confident redesign of microbes and plants for sustainable biofuel production, improved carbon storage, or contaminant bioremediation.”
Project Details
Start Date
2014-11-01
End Date
2015-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members
Related Publications
Ilhan ZE, JK DiBaise, NG Isern, DW Hoyt, AK Marcus, DW Kang, M Crowell, BE Rittmann, and R Krajmalnik-Brown. 2017. "Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding." The ISME Journal 1-12. doi:10.1038/ismej.2017.71
Ilhan Z.E., J.K. DiBaise, S.E. Dautel, N.G. Isern, Y. Kim, D.W. Hoyt, and A.A. Schepmoes, et al. 2020. "Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery." NPJ Biofilms and Microbiomes 6, no. 1:Article No. 12. PNNL-SA-133750. doi:10.1038/s41522-020-0122-5