Lactose drives Enterococcus expansion to promote graft-versus-host disease

被引：231

作者：

Stein-Thoeringer, C. K. ^{[1
,2
,3
]}

Nichols, K. B. ^{[1
,2
]}

Lazrak, A. ^{[1
,2
]}

Docampo, M. D. ^{[1
,2
]}

Slingerland, A. E. ^{[1
,2
]}

Slingerland, J. B. ^{[1
,2
]}

Clurman, A. G. ^{[4
]}

Armijo, G. ^{[1
,2
]}

Gomes, A. L. C. ^{[1
,2
]}

Shono, Y. ^{[1
,2
]}

Staffas, A. ^{[1
,2
]}

da Silva, M. Burgos ^{[1
,2
]}

Devlin, S. M. ^{[5
]}

Markey, K. A. ^{[1
,2
,4
]}

Bajic, D. ^{[6
]}

Pinedo, R. ^{[7
]}

Tsakmaklis, A. ^{[8
,9
]}

Littmann, E. R. ^{[1
,10
]}

Pastore, A. ^{[1
]}

Taur, Y. ^{[11
]}

Monette, S. ^{[12
]}

Arcila, M. E. ^{[13
]}

Pickard, A. J. ^{[14
]}

Maloy, M. ^{[4
]}

Wright, R. J. ^{[1
]}

Amoretti, L. A. ^{[1
]}

Fontana, E. ^{[1
]}

Pham, D. ^{[15
]}

Jamal, M. A. ^{[15
]}

Weber, D. ^{[16
]}

Sung, A. D. ^{[17
]}

Hashimoto, D. ^{[18
]}

Scheid, C. ^{[8
]}

Xavier, J. B. ^{[19
]}

Messina, J. A. ^{[20
]}

Romero, K. ^{[21
]}

Lew, M. ^{[17
]}

Bush, A. ^{[17
]}

Bohannon, L. ^{[17
]}

Hayasaka, K. ^{[22
]}

Hasegawa, Y. ^{[18
]}

Vehreschild, M. J. G. T. ^{[8
,9
,23
]}

Cross, J. R. ^{[14
]}

Ponce, D. M. ^{[2
,4
]}

Perales, M. A. ^{[2
,4
]}

Giralt, S. A. ^{[2
,4
]}

Jenq, R. R. ^{[15
]}

Teshima, T. ^{[18
,22
]}

Holler, E. ^{[16
]}

Chao, N. J. ^{[17
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Immunol, Sloan Kettering Inst, New York, NY 10021 USA

[2] Weill Cornell Med Coll, New York, NY 10065 USA

[3] German Canc Res Ctr, Heidelberg, Germany

[4] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, 1275 York Ave, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA

[6] Tech Univ Munich, Dept Internal Med 2, Munich, Germany

[7] Mem Sloan Kettering Canc Ctr, Gnotobiot Facil, 1275 York Ave, New York, NY 10021 USA

[8] Univ Cologne, Dept Internal Med 1, Ctr Integrated Oncol Aachen Bonn Cologne Duesseld, Cologne, Germany

[9] German Ctr Infect Res, Partner Site Bonn Cologne, Cologne, Germany

[10] Univ Chicago, Dept Med, Sect Infect Med & Global Hlth, 5841 S Maryland Ave, Chicago, IL 60637 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, 1275 York Ave, New York, NY 10021 USA

[12] Rockefeller Univ, Weill Cornell Med, Mem Sloan Kettering Canc Ctr, Lab Comparat Pathol, 1230 York Ave, New York, NY 10021 USA

[13] Mem Sloan Kettering Canc Ctr, Diagnost Mol Pathol Lab, 1275 York Ave, New York, NY 10021 USA

[14] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, 1275 York Ave, New York, NY 10021 USA

[15] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[16] Univ Clin Regensburg, Internal Med 3, Regensburg, Germany

[17] Duke Univ, Med Ctr, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27710 USA

[18] Hokkaido Univ, Dept Hematol, Fac Med, Sapporo, Hokkaido, Japan

[19] Mem Sloan Kettering Canc Ctr, Computat & Syst Biol Program, 1275 York Ave, New York, NY 10021 USA

[20] Duke Univ, Dept Med, Div Infect Dis, Durham, NC USA

[21] Duke Univ, Sch Med, Off Clin Res, Durham, NC USA

[22] Hokkaido Univ Hosp, Div Lab & Transfus Med, Sapporo, Hokkaido, Japan

[23] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Internal Med, Infect Dis, Frankfurt, Germany

来源：

SCIENCE | 2019年 / 366卷 / 6469期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

VANCOMYCIN-RESISTANT ENTEROCOCCUS; CELL; MICROBIOME; BACTEREMIA; RISK; COLONIZATION; CHEMOTHERAPY; ANTIBIOTICS; COMMENSALS; DOMINATION;

D O I：

10.1126/science.aax3760

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

引用

页码：1143 / +

页数：48

共 53 条

[1] Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits [J].

Brandl, Katharina ;

Plitas, George ;

Mihu, Coralia N. ;

Ubeda, Carles ;

Jia, Ting ;

Fleisher, Martin ;

Schnabl, Bernd ;

DeMatteo, Ronald P. ;

Pamer, Eric G. .

NATURE, 2008, 455 (7214) :804-U8

[2] RASTtk: A modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes [J].

Brettin, Thomas ;

Davis, James J. ;

Disz, Terry ;

Edwards, Robert A. ;

Gerdes, Svetlana ;

Olsen, Gary J. ;

Olson, Robert ;

Overbeek, Ross ;

Parrello, Bruce ;

Pusch, Gordon D. ;

Shukla, Maulik ;

Thomason, James A., III ;

Stevens, Rick ;

Vonstein, Veronika ;

Wattam, Alice R. ;

Xia, Fangfang .

SCIENTIFIC REPORTS, 2015, 5

[3] IFNγ differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract [J].

Burman, Angela C. ;

Banovic, Tatjana ;

Kuns, Rachel D. ;

Clouston, Andrew D. ;

Stanley, Amanda C. ;

Morris, Edward S. ;

Rowe, Vanessa ;

Bofinger, Helen ;

Skoczylas, Renae ;

Raffelt, Neil ;

Fahy, Olivier ;

McColl, Shaun R. ;

Engwerda, Christian R. ;

McDonald, Kelli P. A. ;

Hill, Geoffrey R. .

BLOOD, 2007, 110 (03) :1064-1072

[4] Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium [J].

Caballero, Silvia ;

Kim, Sohn ;

Carter, Rebecca A. ;

Leiner, Ingrid M. ;

Susac, Boze ;

Miller, Liza ;

Kim, Grace J. ;

Ling, Lilan ;

Pamer, Eric G. .

CELL HOST & MICROBE, 2017, 21 (05) :592-+

[5] QIIME allows analysis of high-throughput community sequencing data [J].

Caporaso, J. Gregory ;

Kuczynski, Justin ;

Stombaugh, Jesse ;

Bittinger, Kyle ;

Bushman, Frederic D. ;

Costello, Elizabeth K. ;

Fierer, Noah ;

Pena, Antonio Gonzalez ;

Goodrich, Julia K. ;

Gordon, Jeffrey I. ;

Huttley, Gavin A. ;

Kelley, Scott T. ;

Knights, Dan ;

Koenig, Jeremy E. ;

Ley, Ruth E. ;

Lozupone, Catherine A. ;

McDonald, Daniel ;

Muegge, Brian D. ;

Pirrung, Meg ;

Reeder, Jens ;

Sevinsky, Joel R. ;

Tumbaugh, Peter J. ;

Walters, William A. ;

Widmann, Jeremy ;

Yatsunenko, Tanya ;

Zaneveld, Jesse ;

Knight, Rob .

NATURE METHODS, 2010, 7 (05) :335-336

[6] Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB [J].

DeSantis, T. Z. ;

Hugenholtz, P. ;

Larsen, N. ;

Rojas, M. ;

Brodie, E. L. ;

Keller, K. ;

Huber, T. ;

Dalevi, D. ;

Hu, P. ;

Andersen, G. L. .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2006, 72 (07) :5069-5072

[7] Enterococci and Their Interactions with the Intestinal Microbiome [J].

Dubin, Krista ;

Pamer, Eric G. .

MICROBIOLOGY SPECTRUM, 2017, 5 (06)

[8] Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes [J].

Ford, Clyde D. ;

Gazdik, Michaela A. ;

Lopansri, Bert K. ;

Webb, Brandon ;

Mitchell, Birgitta ;

Coombs, Jana ;

Hoda, Daanish ;

Petersen, Finn Bo .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2017, 23 (02) :340-346

[9] The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia [J].

Galloway-Pena, Jessica R. ;

Smith, Daniel P. ;

Sahasrabhojane, Pranoti ;

Ajami, Nadim J. ;

Wadsworth, W. Duncan ;

Daver, Naval G. ;

Chemaly, Roy F. ;

Marsh, Lisa ;

Ghantoji, Shashank S. ;

Pemmaraju, Naveen ;

Garcia-Manero, Guillermo ;

Rezvani, Katayoun ;

Alousi, Amin M. ;

Wargo, Jennifer A. ;

Shpall, Elizabeth J. ;

Futreal, Phillip A. ;

Guindani, Michele ;

Petrosino, Joseph F. ;

Kontoyiannis, Dimitrios P. ;

Shelburne, Samuel A. .

CANCER, 2016, 122 (14) :2186-2196

[10]

GARSIDE P, 1994, IMMUNOLOGY, V82, P211

← 1 2 3 4 5 6 →