title: Quantifying the metabolic activities of human-associated microbial communities across multiple ecological scales.
abstract: Humans are home to complex microbial communities, whose aggregate genomes and their encoded metabolic activities are referred to as the human microbiome. Recently, researchers have begun to appreciate that different human body habitats and the activities of their resident microorganisms can be better understood in ecological terms, as a range of spatial scales encompassing single cells, guilds of microorganisms responsive to a similar substrate, microbial communities, body habitats, and host populations. However, the bulk of the work to date has focused on studies of culturable microorganisms in isolation or on DNA sequencing-based surveys of microbial diversity in small-to-moderate-sized cohorts of individuals. Here, we discuss recent work that highlights the potential for assessing the human microbiome at a range of spatial scales, and for developing novel techniques that bridge multiple levels: for example, through the combination of single-cell methods and metagenomic sequencing. These studies promise to not only provide a much-needed epidemiological and ecological context for mechanistic studies of culturable and genetically tractable microorganisms, but may also lead to the discovery of fundamental rules that govern the assembly and function of host-associated microbial communities.
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: Corinne F
authors.initials: CF
authors.lastname: Maurice
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Turnbaugh
mesh_terms: D000818:Animals; D017753:Ecosystem; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D054892:Metagenome; D056186:Metagenomics / Q000379:methods*; D064307:Microbiota; D059010:Single-Cell Analysis / Q000379:methods
keywords: human microbiome; metabolic activity; metagenomics; microbial ecology; microbiota; single-cell analysis
references.citation: J Allergy Clin Immunol. 2003 Apr;111(4):847-53
references.pmid: 12704368
references.citation: Appl Environ Microbiol. 2005 Aug;71(8):4679-89
references.pmid: 16085863
references.citation: Biol Cell. 1993;78(1-2):1-13
references.pmid: 7693118
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6378-81
references.pmid: 22460792
references.citation: Appl Environ Microbiol. 2011 Nov;77(22):8009-14
references.pmid: 21948826
references.citation: Science. 2010 Apr 9;328(5975):228-31
references.pmid: 20203013
references.citation: Anal Chem. 2004 Jan 1;76(1):40-7
references.pmid: 14697030
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):594-9
references.pmid: 22184244
references.citation: Appl Environ Microbiol. 1999 Jun;65(6):2409-17
references.pmid: 10347021
references.citation: Nature. 2012 Jun 13;486(7402):207-14
references.pmid: 22699609
references.citation: Cell Host Microbe. 2009 Sep 17;6(3):279-89
references.pmid: 19748469
references.citation: Cell Host Microbe. 2011 Nov 17;10(5):507-14
references.pmid: 22036470
references.citation: Anal Biochem. 1999 Mar 15;268(2):278-88
references.pmid: 10075818
references.citation: ISME J. 2010 Sep;4(9):1094-8
references.pmid: 20664551
references.citation: Nature. 2006 Dec 21;444(7122):1027-31
references.pmid: 17183312
references.citation: J Microbiol Methods. 2005 Dec;63(3):276-86
references.pmid: 15935498
references.citation: Appl Environ Microbiol. 1998 Sep;64(9):3336-45
references.pmid: 9726880
references.citation: J Clin Gastroenterol. 2010 May-Jun;44(5):354-60
references.pmid: 20048681
references.citation: Nat Rev Microbiol. 2012 Jul 16;10(8):538-50
references.pmid: 22796884
references.citation: J Clin Microbiol. 1997 Dec;35(12):3181-5
references.pmid: 9399516
references.citation: Appl Environ Microbiol. 2000 Jan;66(1):375-82
references.pmid: 10618251
references.citation: Appl Environ Microbiol. 2003 Sep;69(9):5731-5
references.pmid: 12957972
references.citation: Anal Chem. 2012 Nov 6;84(21):9259-67
references.pmid: 23009651
references.citation: Nat Rev Microbiol. 2005 Jun;3(6):499-504
references.pmid: 15886694
references.citation: Anal Chem. 2004 Aug 1;76(15):4452-8
references.pmid: 15283587
references.citation: Science. 1989 Mar 10;243(4896):1360-3
references.pmid: 2466341
references.citation: Nat Genet. 2008 May;40(5):638-45
references.pmid: 18372903
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7503-8
references.pmid: 20363958
references.citation: Mol Cell Probes. 1988 Jun;2(2):131-45
references.pmid: 3173358
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23
references.pmid: 15505215
references.citation: J Appl Microbiol. 2011 Sep;111(3):616-24
references.pmid: 21672098
references.citation: Lett Appl Microbiol. 2004;39(5):395-400
references.pmid: 15482428
references.citation: Pharmacol Res. 2013 Mar;69(1):21-31
references.pmid: 22902524
references.citation: Biotechniques. 2004 Jul;37(1):46, 48, 50
references.pmid: 15283199
references.citation: Cell Host Microbe. 2012 Oct 18;12(4):509-20
references.pmid: 22999859
references.citation: J Appl Bacteriol. 1996 Feb;80(2):209-15
references.pmid: 8642015
references.citation: J Pediatr Gastroenterol Nutr. 2000 Jan;30(1):61-7
references.pmid: 10630441
references.citation: PLoS Genet. 2011 Feb;7(2):e1001314
references.pmid: 21379339
references.citation: Appl Environ Microbiol. 2000 May;66(5):2199-207
references.pmid: 10788400
references.citation: Cell Host Microbe. 2012 Sep 13;12(3):277-88
references.pmid: 22980325
references.citation: Nature. 2012 Jul 5;487(7405):104-8
references.pmid: 22722865
references.citation: Science. 2007 Sep 14;317(5844):1563-6
references.pmid: 17872448
references.citation: J Adolesc Health. 2004 Aug;35(2):156-8
references.pmid: 15261645
references.citation: Appl Environ Microbiol. 2002 Nov;68(11):5209-16
references.pmid: 12406706
references.citation: Appl Environ Microbiol. 2002 Sep;68(9):4225-32
references.pmid: 12200269
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19786-91
references.pmid: 23150581
references.citation: Environ Sci Pollut Res Int. 2013 May;20(5):2726-34
references.pmid: 23135753
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11971-5
references.pmid: 20566857
references.citation: Nat Biotechnol. 2011 May;29(5):415-20
references.pmid: 21552244
references.citation: Science. 2012 Jun 8;336(6086):1253-5
references.pmid: 22674325
references.citation: Nature. 2010 Mar 4;464(7285):59-65
references.pmid: 20203603
references.citation: Science. 2010 Jul 30;329(5991):533-8
references.pmid: 20671182
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11889-94
references.pmid: 17620602
references.citation: J Raman Spectrosc. 2008 Nov;39(11):1660-1672
references.pmid: 19714262
references.citation: J Microbiol Methods. 2000 Jul;41(2):85-112
references.pmid: 10991623
references.citation: Nature. 2006 Dec 21;444(7122):1022-3
references.pmid: 17183309
references.citation: Front Microbiol. 2011 Apr 27;2:92
references.pmid: 21833331
references.citation: PLoS Comput Biol. 2012;8(7):e1002606
references.pmid: 22807668
references.citation: Methods Enzymol. 2005;397:237-56
references.pmid: 16260295
references.citation: Genome Res. 2012 Oct;22(10):1974-84
references.pmid: 22665442
references.citation: Nature. 2012 May 09;486(7402):222-7
references.pmid: 22699611
references.citation: Appl Environ Microbiol. 2006 Nov;72(11):7022-8
references.pmid: 16950912
references.citation: J Gen Microbiol. 1958 Dec;19(3):592-606
references.pmid: 13611202
references.citation: Genome Res. 2012 Jun;22(6):1107-19
references.pmid: 22434425
references.citation: Appl Environ Microbiol. 1993 Oct;59(10):3187-96
references.pmid: 16349059
references.citation: Science. 2010 Nov 5;330(6005):831-5
references.pmid: 21051639
references.citation: Appl Environ Microbiol. 2000 Dec;66(12):5116-22
references.pmid: 11097877
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):732-7
references.pmid: 16407106
references.citation: Curr Opin Biotechnol. 2003 Jun;14(3):296-302
references.pmid: 12849783
references.citation: FEMS Microbiol Ecol. 2007 Apr;60(1):126-35
references.pmid: 17313661
references.citation: Cytometry. 1993;14(2):136-43
references.pmid: 7679962
references.citation: J Nutr. 2012 Jul;142(7):1205-12
references.pmid: 22623395
references.citation: PLoS One. 2010 Oct 26;5(10):e13633
references.pmid: 21049032
references.citation: Appl Environ Microbiol. 1995 Aug;61(8):3069-75
references.pmid: 7487040
references.citation: PLoS One. 2011;6(7):e22448
references.pmid: 21829462
references.citation: Anal Bioanal Chem. 2009 Jan;393(1):197-206
references.pmid: 18979092
references.citation: Cell Host Microbe. 2008 Apr 17;3(4):213-23
references.pmid: 18407065
references.citation: FEMS Microbiol Rev. 2013 May;37(3):407-27
references.pmid: 23298390
references.citation: Nature. 2009 Jan 22;457(7228):480-4
references.pmid: 19043404
references.citation: Nature. 2012 Oct 4;490(7418):55-60
references.pmid: 23023125
references.citation: FEMS Microbiol Rev. 2012 Mar;36(2):486-511
references.pmid: 22092433
references.citation: Appl Environ Microbiol. 2002 Jan;68(1):114-23
references.pmid: 11772617
references.citation: Biochim Biophys Acta. 2005 Aug 5;1724(3):228-38
references.pmid: 15982822
references.citation: Curr Opin Biotechnol. 2010 Feb;21(1):85-99
references.pmid: 20206495
references.citation: J Microbiol Methods. 1999 Sep;37(3):231-43
references.pmid: 10480267
references.citation: Microbiology (Reading). 2000 May;146 ( Pt 5):1231-1239
references.pmid: 10832651
references.citation: Appl Environ Microbiol. 2005 Feb;71(2):646-55
references.pmid: 15691913
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12204-9
references.pmid: 20566854
references.citation: Appl Environ Microbiol. 1999 Oct;65(10):4475-83
references.pmid: 10508078
references.citation: Cell. 2012 Jun 22;149(7):1578-93
references.pmid: 22726443
references.citation: Microb Ecol. 2007 Apr;53(3):435-42
references.pmid: 17072677
references.citation: ISME J. 2009 Aug;3(8):889-902
references.pmid: 19421234
references.citation: J Biol. 2006;5(6):20
references.pmid: 17010211
references.citation: DNA Res. 2007 Aug 31;14(4):169-81
references.pmid: 17916580
references.citation: Science. 2011 Jan 21;331(6015):337-41
references.pmid: 21205640
references.citation: Cell. 2010 Jun 25;141(7):1135-45
references.pmid: 20602997
references.citation: Science. 2011 May 20;332(6032):974-7
references.pmid: 21512004
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6252-7
references.pmid: 21436049
references.citation: Sci Transl Med. 2013 Mar 27;5(178):178ra41
references.pmid: 23536013
references.citation: Appl Environ Microbiol. 1995 May;61(5):1859-66
references.pmid: 7646023
references.citation: Science. 2012 Jun 8;336(6086):1325-9
references.pmid: 22582016
references.citation: Appl Environ Microbiol. 2008 May;74(10):3143-50
references.pmid: 18359832
references.citation: Environ Microbiol. 2007 Aug;9(8):2050-66
references.pmid: 17635549
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5
references.pmid: 16033867
references.citation: Nat Protoc. 2007;2(4):860-6
references.pmid: 17446886
references.citation: Appl Environ Microbiol. 1999 Apr;65(4):1746-52
references.pmid: 10103276
references.citation: Methods. 2000 Jul;21(3):271-9
references.pmid: 10873481
references.citation: Gut. 2007 May;56(5):661-7
references.pmid: 17047098
references.citation: J Biol Chem. 2011 Jul 22;286(29):25973-82
references.pmid: 21507958
references.citation: Appl Environ Microbiol. 2004 Oct;70(10):5810-7
references.pmid: 15466518
references.citation: PLoS Genet. 2011 Jun;7(6):e1002107
references.pmid: 21698140
references.citation: Nature. 2012 Aug 30;488(7413):621-6
references.pmid: 22914093
references.citation: Science. 2011 Dec 16;334(6062):1518-24
references.pmid: 22174245
references.citation: Curr Opin Biotechnol. 2001 Jun;12(3):231-6
references.pmid: 11404099
references.citation: J Immunol. 2007 Oct 1;179(7):4721-31
references.pmid: 17878371
references.citation: ISME J. 2011 Apr;5(4):627-38
references.pmid: 20981114
references.citation: J Biophotonics. 2009 Feb;2(1-2):70-80
references.pmid: 19343686
references.citation: Science. 2012 Jun 8;336(6086):1251-3
references.pmid: 22674326
references.citation: Appl Microbiol Biotechnol. 1992 Nov;38(2):268-72
references.pmid: 1283525
references.citation: Appl Environ Microbiol. 1992 Jun;58(6):1801-8
references.pmid: 1622256
references.citation: Science. 2009 Dec 18;326(5960):1694-7
references.pmid: 19892944
references.citation: Science. 2011 Jul 1;333(6038):101-4
references.pmid: 21596954
references.citation: Appl Environ Microbiol. 2006 Dec;72(12):7739-47
references.pmid: 17056700
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4599-606
references.pmid: 21317366
references.citation: Sci Transl Med. 2009 Nov 11;1(6):6ra14
references.pmid: 20368178
references.citation: Nature. 2010 Apr 8;464(7290):908-12
references.pmid: 20376150
references.citation: Nature. 2011 Apr 7;472(7341):57-63
references.pmid: 21475195
references.citation: Nature. 2011 May 12;473(7346):174-80
references.pmid: 21508958
references.citation: Annu Rev Genet. 2011;45:431-45
references.pmid: 21942365
references.citation: Scand J Gastroenterol. 1994 Mar;29(3):255-9
references.pmid: 8209186
references.citation: Environ Microbiol. 2007 Aug;9(8):1878-89
references.pmid: 17635536
references.citation: Sci Transl Med. 2011 Oct 26;3(106):106ra106
references.pmid: 22030749
references.citation: Appl Environ Microbiol. 2002 Sep;68(9):4629-36
references.pmid: 12200322
references.citation: Genome Res. 2012 Feb;22(2):292-8
references.pmid: 22009990
references.citation: Appl Environ Microbiol. 2002 Jun;68(6):2982-90
references.pmid: 12039758
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4152-7
references.pmid: 21325608
references.citation: Environ Microbiol. 2007 Jan;9(1):6-7
references.pmid: 17227402
references.citation: Cell. 2013 Jan 17;152(1-2):39-50
references.pmid: 23332745
references.citation: Environ Microbiol Rep. 2009 Feb;1(1):44-9
references.pmid: 23765719
references.citation: Genome Res. 2009 Apr;19(4):636-43
references.pmid: 19251737
references.citation: J Biol Chem. 2012 Oct 5;287(41):34614-25
references.pmid: 22910908
references.citation: Annu Rev Microbiol. 2009;63:411-29
references.pmid: 19514853
references.citation: Int J Obes (Lond). 2013 Jan;37(1):16-23
references.pmid: 22907693
references.citation: Appl Microbiol Biotechnol. 1993 May;39(2):254-8
references.pmid: 7763732
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Oct 1;66(Pt 10):1261-4
references.pmid: 20944220
references.citation: Cell. 2009 Oct 30;139(3):485-98
references.pmid: 19836068
references.citation: PLoS Biol. 2011 Dec;9(12):e1001221
references.pmid: 22205877
references.citation: Science. 2005 Jun 10;308(5728):1635-8
references.pmid: 15831718
references.citation: Appl Environ Microbiol. 1995 Jul;61(7):2696-701
references.pmid: 16535078
references.citation: FEMS Microbiol Ecol. 2003 Mar 1;43(2):237-45
references.pmid: 19719684
references.citation: Science. 2006 Jun 2;312(5778):1355-9
references.pmid: 16741115
references.citation: Microbiol Rev. 1995 Mar;59(1):143-69
references.pmid: 7535888
references.citation: Appl Environ Microbiol. 2001 May;67(5):2240-7
references.pmid: 11319107
references.citation: J Nutr. 2008 Jul;138(7):1310-6
references.pmid: 18567753