Metabolomics of Mixed Microbial Communities: Understanding the Influence of Gut Microbiota on Host Energy Regulation.
EMSL Project ID
48159
Abstract
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 propose to utilize EMSL’s NMR metabolomics capability to study role of human intestinal microbiota on weight loss subsequent to a common method of bariatric surgery: the Roux-en-Y gastric bypass (RYGB). The hypothesis to be tested is that successful surgical weight loss is linked with alterations in intestinal microflora and in utilization of microbial H2-consumption pathway, including a reduction in one or more H2-oxidizing microorganisms that results in differences in microbial metabolism and a unique fecal microbiome-derived metabolome. Malabsorption in the small intestine subsequent to RYGB increases the carbohydrate, lipid, and protein concentrations in the large intestine. Successful weight loss may be linked to an increase in digestible polysaccharides (i.e., starch) in the colon, changing the intestinal environment, which may then alter gut microbiota and utilization of microbial fermentation pathways. Nuclear magnetic resonance is ideal for the detection and quantification of low molecular weight metabolites and will provide vital information to augment the parent grant. We plan to evaluate luminal gut microbiota in 30 RYGB patients, 10 healthy controls, and 10 obese patients, focusing on differences between individuals who demonstrate successful versus unsuccessful weight loss (defined in the parent proposal body). 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, thus fulfilling the EMSL mission, to provide “integrated experimental and computational resources for discovery and technological innovation in the environmental molecular sciences to support the needs of DOE and the nation.” 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.
Project Details
Start Date
2013-10-24
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
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