Advertisement

The Intestinal Metabolome: An Intersection Between Microbiota and Host

      Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person’s physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, the computational challenges in integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future data sets.

      Keywords

      Abbreviation used in this paper:

      PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Tringe S.G.
        • Hugenholtz P.
        A renaissance for the pioneering 16S rRNA gene.
        Curr Opin Microbiol. 2008; 11: 442-446
        • Dominguez–Bello M.G.
        • Blaser M.J.
        • Ley R.E.
        • et al.
        Development of the human gastrointestinal microbiota and insights from high-throughput sequencing.
        Gastroenterology. 2011; 140: 1713-1719
        • Ursell L.K.
        • Van Treuren W.
        • Metcalf J.L.
        • et al.
        Replenishing our defensive microbes.
        Bioessays. 2013; 35: 810-817
        • Song S.J.
        • Lauber C.
        • Costello E.K.
        • et al.
        Cohabiting family members share microbiota with one another and with their dogs.
        Elife. 2013; 2: e00458
        • Wu G.D.
        • Chen J.
        • Hoffmann C.
        • et al.
        Linking long-term dietary patterns with gut microbial enterotypes.
        Science. 2011; 334: 105-108
        • David L.A.
        • Maurice C.F.
        • Carmody R.N.
        • et al.
        Diet rapidly and reproducibly alters the human gut microbiome.
        Nature. 2014; 505: 559-563
        • Benson A.K.
        • Kelly S.A.
        • Legge R.
        • et al.
        Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.
        Proc Natl Acad Sci U S A. 2010; 107: 18933-18938
        • Caporaso J.G.
        • Lauber C.L.
        • Costello E.K.
        • et al.
        Moving pictures of the human microbiome.
        Genome Biol. 2011; 12: R50
        • Costello E.K.
        • Lauber C.L.
        • Hamady M.
        • et al.
        Bacterial community variation in human body habitats across space and time.
        Science. 2009; 326: 1694-1697
        • Human Microbiome Project Consortium
        Structure, function and diversity of the healthy human microbiome.
        Nature. 2012; 486: 207-214
        • Qin J.
        • Li R.
        • Raes J.
        • et al.
        A human gut microbial gene catalogue established by metagenomic sequencing.
        Nature. 2010; 464: 59-65
        • Haiser H.J.
        • Turnbaugh P.J.
        Is it time for a metagenomic basis of therapeutics?.
        Science. 2012; 336: 1253-1255
        • Maurice C.F.
        • Haiser H.J.
        • Turnbaugh P.J.
        Xenobiotics shape the physiology and gene expression of the active human gut microbiome.
        Cell. 2013; 152: 39-50
        • McNulty N.P.
        • Yatsunenko T.
        • Hsiao A.
        • et al.
        The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.
        Sci Transl Med. 2011; 3 (106ra106)
        • Marcobal A.
        • Kashyap P.C.
        • Nelson T.A.
        • et al.
        A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice.
        ISME J. 2013; 7: 1933-1943
        • Penders J.
        • Stobberingh E.E.
        • Savelkoul P.H.
        • et al.
        The human microbiome as a reservoir of antimicrobial resistance.
        Front Microbiol. 2013; 4: 87
        • Rasko D.A.
        • Rosovitz M.J.
        • Myers G.S.
        • et al.
        The pangenome structure of Escherichia coli: comparative genomic analysis of E. coli commensal and pathogenic isolates.
        J Bacteriol. 2008; 190: 6881-6893
        • Cryan J.F.
        • Dinan T.G.
        Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.
        Nat Rev Neurosci. 2012; 13: 701-712
        • Dettmer K.
        • Aronov P.A.
        • Hammock B.D.
        Mass spectrometry-based metabolomics.
        Mass Spectrom Rev. 2007; 26: 51-78
        • Slupsky C.M.
        Nuclear magnetic resonance-based analysis of urine for the rapid etiological diagnosis of pneumonia.
        Expert Opin Med Diagn. 2011; 5: 63-73
        • Rath C.M.
        • Alexandrov T.
        • Higginbottom S.K.
        • et al.
        Molecular analysis of model gut microbiotas by imaging mass spectrometry and nanodesorption electrospray ionization reveals dietary metabolite transformations.
        Anal Chem. 2012; 84: 9259-9267
        • Watrous J.
        • Roach P.
        • Alexandrov T.
        • et al.
        Mass spectral molecular networking of living microbial colonies.
        Proc Natl Acad Sci U S A. 2012; 109: E1743-E1752
        • Wishart D.S.
        • Jewison T.
        • Guo A.C.
        • et al.
        HMDB 3.0—the Human Metabolome Database in 2013.
        Nucleic Acids Res. 2013; 41: D801-D817
        • Smith C.A.
        • O'Maille G.
        • Want E.J.
        • et al.
        METLIN: a metabolite mass spectral database.
        Ther Drug Monit. 2005; 27: 747-751
        • Sud M.
        • Fahy E.
        • Cotter D.
        • et al.
        LMSD: LIPID MAPS structure database.
        Nucleic Acids Res. 2007; 35: D527-D532
        • Horai H.
        • Arita M.
        • Kanaya S.
        • et al.
        MassBank: a public repository for sharing mass spectral data for life sciences.
        J Mass Spectrom. 2010; 45: 703-714
        • Stein S.E.
        Chemical substructure identification by mass spectral library searching.
        J Am Soc Mass Spectrom. 1995; 6: 644-655
        • Yang J.Y.
        • Sanchez L.M.
        • Rath C.M.
        • et al.
        Molecular networking as a dereplication strategy.
        J Nat Prod. 2013; 76: 1686-1699
        • Wikoff W.R.
        • Anfora A.T.
        • Liu J.
        • et al.
        Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.
        Proc Natl Acad Sci U S A. 2009; 106: 3698-3703
        • Martin F.P.
        • Sprenger N.
        • Yap I.K.
        • et al.
        Panorganismal gut microbiome-host metabolic crosstalk.
        J Proteome Res. 2009; 8: 2090-2105
        • Machiels K.
        • Joossens M.
        • Sabino J.
        • et al.
        A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis.
        Gut. 2013 Sep 10; ([Epub ahead of print])
        • Wang W.
        • Chen L.
        • Zhou R.
        • et al.
        Increased proportion of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease.
        J Clin Microbiol. 2014; 52: 398-406
        • Le Chatelier E.
        • Nielsen T.
        • Qin J.
        • et al.
        Richness of human gut microbiome correlates with metabolic markers.
        Nature. 2013; 500: 541-546
        • Turnbaugh P.J.
        • Hamady M.
        • Yatsunenko T.
        • et al.
        A core gut microbiome in obese and lean twins.
        Nature. 2009; 457: 480-484
        • Fang S.
        • Evans R.M.
        Microbiology: wealth management in the gut.
        Nature. 2013; 500: 538-539
        • Langille M.G.
        • Zaneveld J.
        • Caporaso J.G.
        • et al.
        Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences.
        Nat Biotechnol. 2013; 31: 814-821
        • Larsen N.
        • Vogensen F.K.
        • van den Berg F.W.
        • et al.
        Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.
        PLoS One. 2010; 5: e9085
        • Heederik D.
        • von Mutius E.
        Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma?.
        J Allergy Clin Immunol. 2012; 130: 44-50
        • Blaser M.
        Antibiotic overuse: Stop the killing of beneficial bacteria.
        Nature. 2011; 476: 393-394
        • Sellitto M.
        • Bai G.
        • Serena G.
        • et al.
        Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.
        PLoS One. 2012; 7: e33387
        • Yatsunenko T.
        • Rey F.E.
        • Manary M.J.
        • et al.
        Human gut microbiome viewed across age and geography.
        Nature. 2012; 486: 222-227
        • Sela D.A.
        • Chapman J.
        • Adeuya A.
        • et al.
        The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome.
        Proc Natl Acad Sci U S A. 2008; 105: 18964-18969
        • Scheline R.R.
        Metabolism of foreign compounds by gastrointestinal microorganisms.
        Pharmacol Rev. 1973; 25: 451-523
        • Goldman P.
        • Peppercorn M.A.
        • Goldin B.R.
        Metabolism of drugs by microorganisms in the intestine.
        Am J Clin Nutr. 1974; 27: 1348-1355
        • Goldman P.
        Biochemical pharmacology of the intestinal flora.
        Annu Rev Pharmacol Toxicol. 1978; 18: 523-539
        • Clayton T.A.
        • Baker D.
        • Lindon J.C.
        • et al.
        Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.
        Proc Natl Acad Sci U S A. 2009; 106: 14728-14733
        • Claus S.P.
        • Ellero S.L.
        • Berger B.
        • et al.
        Colonization-induced host-gut microbial metabolic interaction.
        MBio. 2011; 2 (e00271–10)
        • Sousa T.
        • Paterson R.
        • Moore V.
        • et al.
        The gastrointestinal microbiota as a site for the biotransformation of drugs.
        Int J Pharm. 2008; 363: 1-25
        • Haiser H.J.
        • Turnbaugh P.J.
        Developing a metagenomic view of xenobiotic metabolism.
        Pharmacol Res. 2013; 69: 21-31
        • Saha J.R.
        • Butler Jr., V.P.
        • Neu H.C.
        • et al.
        Digoxin-inactivating bacteria: identification in human gut flora.
        Science. 1983; 220: 325-327
        • Haiser H.J.
        • Gootenberg D.B.
        • Chatman K.
        • et al.
        Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta.
        Science. 2013; 341: 295-298
        • Sperry J.F.
        • Wilkins T.D.
        Arginine, a growth-limiting factor for Eubacterium lentum.
        J Bacteriol. 1976; 127: 780-784
        • Wallace B.D.
        • Wang H.
        • Lane K.T.
        • et al.
        Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.
        Science. 2010; 330: 831-835
        • Iida N.
        • Dzutsev A.
        • Stewart C.A.
        • et al.
        Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.
        Science. 2013; 342: 967-970
        • Viaud S.
        • Saccheri F.
        • Mignot G.
        • et al.
        The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.
        Science. 2013; 342: 971-976
        • Friedman J.
        • Alm E.J.
        Inferring correlation networks from genomic survey data.
        PLoS Comput Biol. 2012; 8: e1002687
        • Faust K.
        • Sathirapongsasuti J.F.
        • Izard J.
        • et al.
        Microbial co-occurrence relationships in the human microbiome.
        PLoS Comput Biol. 2012; 8: e1002606