Molecular analysis of model gut microbiotas by imaging mass spectrometry and nanodesorption electrospray ionization reveals dietary metabolite transformations.

The communities constituting our microbiotas are emerging as mediators of the health-disease continuum. However, deciphering the functional impact of microbial communities on host pathophysiology represents a formidable challenge, due to the heterogeneous distribution of chemical and microbial species within the gastrointestinal (GI) tract. Herein, we apply imaging mass spectrometry (IMS) to localize metabolites from the interaction between the host and colonizing microbiota. This approach complements other molecular imaging methodologies in that analytes need not be known a priori, offering the possibility of untargeted analysis. Localized molecules within the GI tract were then identified in situ by surface sampling with nanodesorption electrospray ionization Fourier transform ion cyclotron resonance-mass spectrometry (nanoDESI FTICR-MS). Products from diverse structural classes were identified including cholesterol-derived lipids, glycans, and polar metabolites. Specific chemical transformations performed by the microbiota were validated with bacteria in culture. This study illustrates how untargeted spatial characterization of metabolites can be applied to the molecular dissection of complex biology in situ.

[1]  A. S. Attia,et al.  Monitoring the inflammatory response to infection through the integration of MALDI IMS and MRI. , 2012, Cell host & microbe.

[2]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[3]  Nuno Bandeira,et al.  Mass spectral molecular networking of living microbial colonies , 2012, Proceedings of the National Academy of Sciences.

[4]  G. Siuzdak,et al.  Innovation: Metabolomics: the apogee of the omics trilogy , 2012, Nature Reviews Molecular Cell Biology.

[5]  Ludovic C. Gillet,et al.  Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis* , 2012, Molecular & Cellular Proteomics.

[6]  B. Weimer,et al.  Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. , 2011, Cell host & microbe.

[7]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[8]  Richard M Caprioli,et al.  MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives. , 2011, Trends in biotechnology.

[9]  Jeramie D Watrous,et al.  The evolving field of imaging mass spectrometry and its impact on future biological research. , 2011, Journal of mass spectrometry : JMS.

[10]  M. Hattori,et al.  Bifidobacteria can protect from enteropathogenic infection through production of acetate , 2011, Nature.

[11]  Theodore Alexandrov,et al.  Spatial segmentation of imaging mass spectrometry data with edge-preserving image denoising and clustering. , 2010, Journal of proteome research.

[12]  S. Böcker,et al.  Computational mass spectrometry for metabolomics: Identification of metabolites and small molecules , 2010, Analytical and bioanalytical chemistry.

[13]  E. Want,et al.  Systemic gut microbial modulation of bile acid metabolism in host tissue compartments , 2010, Proceedings of the National Academy of Sciences.

[14]  Julia Laskin,et al.  Nanospray desorption electrospray ionization: an ambient method for liquid-extraction surface sampling in mass spectrometry. , 2010, The Analyst.

[15]  M. Hirai,et al.  MassBank: a public repository for sharing mass spectral data for life sciences. , 2010, Journal of mass spectrometry : JMS.

[16]  B. Finlay,et al.  Gut microbiota in health and disease. , 2010, Physiological reviews.

[17]  J. Sonnenburg,et al.  Specificity of Polysaccharide Use in Intestinal Bacteroides Species Determines Diet-Induced Microbiota Alterations , 2010, Cell.

[18]  Laxman Yetukuri,et al.  The gut microbiota modulates host energy and lipid metabolism in mice[S] , 2010, Journal of Lipid Research.

[19]  Pieter C. Dorrestein,et al.  Translating metabolic exchange with imaging mass spectrometry , 2009, Nature chemical biology.

[20]  J. Gordon,et al.  Coordinate Regulation of Glycan Degradation and Polysaccharide Capsule Biosynthesis by a Prominent Human Gut Symbiont , 2009, The Journal of Biological Chemistry.

[21]  W. R. Wikoff,et al.  Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites , 2009, Proceedings of the National Academy of Sciences.

[22]  Ara Darzi,et al.  The human gut microbiome: Implications for future health care , 2008, Current gastroenterology reports.

[23]  Elaine Holmes,et al.  Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes , 2008, Molecular systems biology.

[24]  H. Harizi,et al.  Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. , 2008, Trends in molecular medicine.

[25]  Colin Hill,et al.  Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome , 2008, Proceedings of the National Academy of Sciences.

[26]  Johan Auwerx,et al.  Targeting bile-acid signalling for metabolic diseases , 2008, Nature Reviews Drug Discovery.

[27]  R. Murphy,et al.  Sublimation as a method of matrix application for mass spectrometric imaging , 2007, Journal of the American Society for Mass Spectrometry.

[28]  D. Darmaun,et al.  Intestinal Microbiota in Neonates and Preterm Infants: A Review , 2007 .

[29]  C. Press Cell host & microbe , 2007 .

[30]  J. Gordon,et al.  Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host , 2006, PLoS biology.

[31]  Keiko Nagata,et al.  Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria , 2006, Lipids.

[32]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[33]  R. Abagyan,et al.  XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. , 2006, Analytical chemistry.

[34]  H. Nakao,et al.  Deconjugation of bile acids by human intestinal bacteria implanted in germ-free rats , 1987, Lipids.

[35]  Benjamin P. Westover,et al.  Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont , 2005, Science.

[36]  K. Barrett,et al.  Enteroinvasive bacteria alter barrier and transport properties of human intestinal epithelium: role of iNOS and COX-2. , 2002, Gastroenterology.

[37]  J. Ritter Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. , 2000, Chemico-biological interactions.

[38]  A. Lorenz,et al.  Degradation of Pectins with Different Degrees of Esterification by Bacteroides thetaiotaomicron Isolated from Human Gut Flora , 2000, Applied and Environmental Microbiology.

[39]  A. Medici,et al.  Biotransformations on steroid nucleus of bile acids , 1997, Steroids.

[40]  F. Schneider,et al.  Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536 , 1995, Applied and environmental microbiology.

[41]  R. Edenharder Dehydroxylation of cholic acid at C12 and epimerization at C5 and C7 by Bacteroides species. , 1984, Journal of steroid biochemistry.