title: Anoxic Conditions Promote Species-Specific Mutualism between Gut Microbes In Silico.
abstract: The human gut is inhabited by thousands of microbial species, most of which are still uncharacterized. Gut microbes have adapted to each other's presence as well as to the host and engage in complex cross feeding. Constraint-based modeling has been successfully applied to predicting microbe-microbe interactions, such as commensalism, mutualism, and competition. Here, we apply a constraint-based approach to model pairwise interactions between 11 representative gut microbes. Microbe-microbe interactions were computationally modeled in conjunction with human small intestinal enterocytes, and the microbe pairs were subjected to three diets with various levels of carbohydrate, fat, and protein in normoxic or anoxic environments. Each microbe engaged in species-specific commensal, parasitic, mutualistic, or competitive interactions. For instance, Streptococcus thermophilus efficiently outcompeted microbes with which it was paired, in agreement with the domination of streptococci in the small intestinal microbiota. Under anoxic conditions, the probiotic organism Lactobacillus plantarum displayed mutualistic behavior toward six other species, which, surprisingly, were almost entirely abolished under normoxic conditions. This finding suggests that the anoxic conditions in the large intestine drive mutualistic cross feeding, leading to the evolvement of an ecosystem more complex than that of the small intestinal microbiota. Moreover, we predict that the presence of the small intestinal enterocyte induces competition over host-derived nutrients. The presented framework can readily be expanded to a larger gut microbial community. This modeling approach will be of great value for subsequent studies aiming to predict conditions favoring desirable microbes or suppressing pathogens.
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.
authors.forename: Almut
authors.initials: A
authors.lastname: Heinken
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg Faculty of Science, Technology and Communication, University of Luxembourg, Belval, Luxembourg ines.thiele@uni.lu.
authors.forename: Ines
authors.initials: I
authors.lastname: Thiele
mesh_terms: D000693:Anaerobiosis; D003198:Computer Simulation; D004032:Diet; D020895:Enterocytes / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D056265:Microbial Interactions; D064307:Microbiota; D010100:Oxygen; D013045:Species Specificity; D048249:Streptococcus thermophilus / Q000254:growth & development; D013559:Symbiosis
chemical_list: D010100:Oxygen
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10011-6
references.pmid: 16782812
references.citation: Appl Microbiol Biotechnol. 2013 Oct;97(19):8729-39
references.pmid: 23974365
references.citation: Nat Protoc. 2011 Sep;6(9):1290-307
references.pmid: 21886097
references.citation: PLoS Pathog. 2013;9(11):e1003730
references.pmid: 24278012
references.citation: Science. 2012 Jun 8;336(6086):1262-7
references.pmid: 22674330
references.citation: J Biol Chem. 2006 Dec 29;281(52):40041-8
references.pmid: 17062565
references.citation: Curr Opin Microbiol. 2014 Apr;18:72-7
references.pmid: 24632350
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14482-7
references.pmid: 18787117
references.citation: Environ Microbiol. 2014 Sep;16(9):2915-26
references.pmid: 24118739
references.citation: Biotechnol Bioeng. 2012 Oct;109(10):2475-83
references.pmid: 22510989
references.citation: Cell Metab. 2014 Nov 4;20(5):742-52
references.pmid: 25176148
references.citation: Appl Environ Microbiol. 2014 Jan;80(2):788-96
references.pmid: 24242251
references.citation: PLoS Comput Biol. 2012 Feb;8(2):e1002363
references.pmid: 22319433
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5859-64
references.pmid: 19321416
references.citation: Mol Syst Biol. 2010 Sep 7;6:407
references.pmid: 20823845
references.citation: J Bacteriol. 2014 Sep;196(18):3289-302
references.pmid: 25002542
references.citation: Annu Rev Nutr. 2002;22:283-307
references.pmid: 12055347
references.citation: Science. 2012 May 4;336(6081):601-4
references.pmid: 22556256
references.citation: PLoS Comput Biol. 2010;6(11):e1001002
references.pmid: 21124952
references.citation: PLoS One. 2011;6(12):e28789
references.pmid: 22216112
references.citation: BMC Syst Biol. 2011;5:182
references.pmid: 22044664
references.citation: Gut Microbes. 2013 Jan-Feb;4(1):28-40
references.pmid: 23022739
references.citation: ISME J. 2013 Jul;7(7):1256-61
references.pmid: 23677008
references.citation: Appl Environ Microbiol. 2002 Oct;68(10):5186-90
references.pmid: 12324374
references.citation: Appl Environ Microbiol. 2009 Jun;75(11):3627-33
references.pmid: 19346354
references.citation: Pharmacol Res. 2013 Mar;69(1):52-60
references.pmid: 23147033
references.citation: PLoS Biol. 2011 Dec;9(12):e1001221
references.pmid: 22205877
references.citation: J Bacteriol. 2011 Apr;193(7):1710-7
references.pmid: 21296962
references.citation: Gut Microbes. 2015;6(2):120-30
references.pmid: 25901891
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12804-9
references.pmid: 23858463
references.citation: Int J Food Microbiol. 2004 Nov 15;96(3):219-33
references.pmid: 15454313
references.citation: Microbiome. 2013 May 03;1(1):14
references.pmid: 24450613
references.citation: Environ Microbiol. 2007 May;9(5):1101-11
references.pmid: 17472627
references.citation: PLoS One. 2013;8(10):e77617
references.pmid: 24204896
references.citation: ISME J. 2011 Feb;5(2):305-16
references.pmid: 20668487
references.citation: Free Radic Biol Med. 2013 Feb;55:130-40
references.pmid: 23127782
references.citation: Nat Commun. 2011;2:589
references.pmid: 22158444
references.citation: Biophys J. 2010 May 19;98(10):2072-81
references.pmid: 20483314
references.citation: Science. 2005 Jun 10;308(5728):1635-8
references.pmid: 15831718
references.citation: Nature. 2010 Mar 4;464(7285):59-65
references.pmid: 20203603
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4586-91
references.pmid: 10200306
references.citation: Sci Transl Med. 2014 Jan 22;6(220):220ra11
references.pmid: 24452263
references.citation: Curr Opin Biotechnol. 2013 Feb;24(1):4-12
references.pmid: 23102866
references.citation: Nat Rev Microbiol. 2012 May;10(5):366-72
references.pmid: 22450377
references.citation: Cell Microbiol. 2011 Feb;13(2):171-6
references.pmid: 21166974
references.citation: BMC Microbiol. 2014;14:133
references.pmid: 24884540
references.citation: BMC Bioinformatics. 2010;11:489
references.pmid: 20920235
references.citation: Nutr Rev. 2013 Jul;71(7):483-99
references.pmid: 23815146
references.citation: J Bacteriol. 2005 Aug;187(16):5818-30
references.pmid: 16077130
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20338-43
references.pmid: 24277855
references.citation: Nat Biotechnol. 2010 Mar;28(3):245-8
references.pmid: 20212490
references.citation: ISME J. 2012 Jul;6(7):1415-26
references.pmid: 22258098
references.citation: FEMS Microbiol Lett. 2006 Jan;254(1):116-22
references.pmid: 16451188
references.citation: J Biol Chem. 2010 Jul 16;285(29):22082-90
references.pmid: 20444704
references.citation: Appl Environ Microbiol. 2006 May;72(5):3593-9
references.pmid: 16672507
references.citation: Curr Opin Gastroenterol. 2014 Mar;30(2):120-7
references.pmid: 24468803
references.citation: Hum Mol Genet. 2013 Jul 1;22(13):2705-22
references.pmid: 23492669
references.citation: J AOAC Int. 2012 Jan-Feb;95(1):50-60
references.pmid: 22468341
references.citation: BMC Syst Biol. 2011;5:8
references.pmid: 21244678
references.citation: Proteomics. 2008 Apr;8(8):1661-76
references.pmid: 18409168