title: Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity.
abstract: Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
authors.affiliation: Obesity, Metabolism & Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Alice P
authors.initials: AP
authors.lastname: Liou
authors.forename: Melissa
authors.initials: M
authors.lastname: Paziuk
authors.forename: Jesus-Mario
authors.initials: JM
authors.lastname: Luevano
authors.forename: Sriram
authors.initials: S
authors.lastname: Machineni
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Turnbaugh
authors.forename: Lee M
authors.initials: LM
authors.lastname: Kaplan
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D004435:Eating / Q000502:physiology; D015390:Gastric Bypass; D041981:Gastrointestinal Tract / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
references.citation: Ann N Y Acad Sci. 2010 Nov;1212:E37-45
references.pmid: 21732953
references.citation: Nature. 2006 Jan 26;439(7075):484-9
references.pmid: 16400329
references.citation: Endocrinology. 2009 Jun;150(6):2518-25
references.pmid: 19372197
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4516-22
references.pmid: 20534432
references.citation: Gut Microbes. 2012 Jul-Aug;3(4):279-88
references.pmid: 22572877
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16767-72
references.pmid: 18931303
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5
references.pmid: 16033867
references.citation: Genome Biol. 2011 Jun 24;12(6):R60
references.pmid: 21702898
references.citation: BMC Microbiol. 2008 May 20;8:79
references.pmid: 18492229
references.citation: Br J Nutr. 2013 May 28;109(10):1755-64
references.pmid: 23110765
references.citation: J Clin Endocrinol Metab. 2011 Oct;96(10):E1630-3
references.pmid: 21832118
references.citation: Transl Res. 2013 Mar;161(3):131-40
references.pmid: 23146568
references.citation: Front Microbiol. 2011 Aug 01;2:166
references.pmid: 21904534
references.citation: Science. 2010 Apr 9;328(5975):228-31
references.pmid: 20203013
references.citation: Appl Environ Microbiol. 1996 Feb;62(2):668-75
references.pmid: 8593069
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):594-9
references.pmid: 22184244
references.citation: Ann Surg. 2006 Jan;243(1):108-14
references.pmid: 16371744
references.citation: Obesity (Silver Spring). 2012 Apr;20(4):738-47
references.pmid: 21593810
references.citation: J Lipid Res. 1967 Nov;8(6):682-7
references.pmid: 6057497
references.citation: Nature. 2006 Dec 21;444(7122):1027-31
references.pmid: 17183312
references.citation: Diabetes. 2010 Dec;59(12):3049-57
references.pmid: 20876719
references.citation: Science. 2008 Jun 20;320(5883):1647-51
references.pmid: 18497261
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84
references.pmid: 17210919
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23
references.pmid: 15505215
references.citation: Gut. 2011 Sep;60(9):1214-23
references.pmid: 21572120
references.citation: Biochim Biophys Acta. 2010 Nov;1801(11):1175-83
references.pmid: 20691280
references.citation: ISME J. 2012 Aug;6(8):1621-4
references.pmid: 22402401
references.citation: Nature. 2012 Jul 5;487(7405):104-8
references.pmid: 22722865
references.citation: Ann Surg. 2004 Aug;240(2):236-42
references.pmid: 15273546
references.citation: Environ Microbiol. 2009 Aug;11(8):2112-22
references.pmid: 19397676
references.citation: Endocrinology. 2012 May;153(5):2234-44
references.pmid: 22416083
references.citation: Physiol Rev. 1990 Apr;70(2):567-90
references.pmid: 2181501
references.citation: J Clin Endocrinol Metab. 2012 Jun;97(6):E1023-31
references.pmid: 22492873
references.citation: Am J Clin Nutr. 1991 Mar;53(3):681-7
references.pmid: 2000822
references.citation: Endocrinology. 2005 Dec;146(12):5092-9
references.pmid: 16123168
references.citation: Gastroenterology. 2009 Nov;137(5):1716-24.e1-2
references.pmid: 19706296
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2365-70
references.pmid: 19164560
references.citation: Cell Host Microbe. 2008 Apr 17;3(4):213-23
references.pmid: 18407065
references.citation: Nature. 2009 Jan 22;457(7228):480-4
references.pmid: 19043404
references.citation: Science. 2005 Mar 25;307(5717):1915-20
references.pmid: 15790844
references.citation: ISME J. 2012 Aug;6(8):1449-58
references.pmid: 22437156
references.citation: Gastroenterology. 2010 May;138(5):1845-53
references.pmid: 19931268
references.citation: Diabetologia. 2012 Aug;55(8):2285-94
references.pmid: 22572803
references.citation: Physiol Behav. 2004 Apr;81(2):243-8
references.pmid: 15159170
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6
references.pmid: 20679230
references.citation: Appl Environ Microbiol. 2000 May;66(5):2166-74
references.pmid: 10788396
references.citation: J AOAC Int. 2012 Jan-Feb;95(1):50-60
references.pmid: 22468341
references.citation: Annu Rev Med. 2010;61:393-411
references.pmid: 20059345
references.citation: J Surg Res. 2013 Jan;179(1):e91-8
references.pmid: 22504136
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: Nutr Rev. 2010 Aug;68(8):459-64
references.pmid: 20646223
references.citation: Nat Methods. 2010 May;7(5):335-6
references.pmid: 20383131
references.citation: J Clin Endocrinol Metab. 2008 Dec;93(12):4656-63
references.pmid: 18765510
references.citation: Proc Natl Acad Sci U S A. 2011 May 10;108(19):8030-5
references.pmid: 21518883
references.citation: Obesity (Silver Spring). 2009 Oct;17(10):1839-47
references.pmid: 19556976