The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD

被引：111

作者：

Markey, Kate A. ^{[1
,2
]}

Schluter, Jonas ^{[3
]}

Gomes, Antonio L. C. ^{[4
]}

Littmann, Eric R. ^{[4
]}

Pickard, Amanda J. ^{[5
]}

Taylor, Bradford P. ^{[3
]}

Giardina, Paul A. ^{[1
,4
]}

Weber, Daniela ^{[5
]}

Dai, Anqi ^{[4
]}

Docampo, Melissa D. ^{[2
,4
]}

Armijo, Gabriel K. ^{[4
]}

Slingerland, Ann E. ^{[4
]}

Slingerland, John B. ^{[1
]}

Nichols, Katherine B. ^{[4
]}

Brereton, Daniel G. ^{[1
]}

Clurman, Annelie G. ^{[1
]}

Ramos, Ruben J. ^{[6
]}

Rao, Arka ^{[6
]}

Bush, Amy ^{[7
]}

Bohannon, Lauren ^{[7
]}

Covington, Megan ^{[7
]}

Lew, Meagan V. ^{[7
]}

Rizzieri, David A. ^{[7
]}

Chao, Nelson ^{[7
]}

Maloy, Molly ^{[1
]}

Cho, Christina ^{[1
,2
]}

Politikos, Ioannis ^{[1
,2
]}

Giralt, Sergio ^{[1
,2
]}

Taur, Ying ^{[2
,8
]}

Pamer, Eric G. ^{[2
,4
,8
]}

Holler, Ernst ^{[5
]}

Perales, Miguel-Angel ^{[1
,2
]}

Ponce, Doris M. ^{[1
]}

Devlin, Sean M. ^{[9
]}

Xavier, Joao ^{[3
]}

Sung, Anthony D. ^{[7
]}

Peled, Jonathan U. ^{[1
,2
]}

Cross, Justin R. ^{[6
]}

van den Brink, Marcel R. M. ^{[1
,2
,4
]}

机构：

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

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

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

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

[5] Univ Med Ctr, Internal Med 3, Dept Hematol & Oncol, Regensburg, Germany

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

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

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

[9] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

来源：

BLOOD | 2020年 / 136卷 / 01期

基金：

美国国家卫生研究院;

关键词：

VERSUS-HOST-DISEASE; GUT MICROBIOME; CELL;

D O I：

10.1182/blood.2019003369

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant pa-tients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immuno-modulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.

引用

页码：130 / 136

页数：7

共 33 条

[1]

[Anonymous], 2018, Package 'vegan'

[2] Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation [J].

Arora, Mukta ;

Cutler, Corey S. ;

Jagasia, Madan H. ;

Pidala, Joseph ;

Chai, Xiaoyu ;

Martin, Paul J. ;

Flowers, Mary E. D. ;

Inamoto, Yoshihiro ;

Chen, George L. ;

Wood, William A. ;

Khera, Nandita ;

Palmer, Jeanne ;

Duong, Hien ;

Arai, Sally ;

Mayer, Sebastian ;

Pusic, Iskra ;

Lee, Stephanie J. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (03) :449-455

[3] Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation [J].

Arpaia, Nicholas ;

Campbell, Clarissa ;

Fan, Xiying ;

Dikiy, Stanislav ;

van der Veeken, Joris ;

deRoos, Paul ;

Liu, Hui ;

Cross, Justin R. ;

Pfeffer, Klaus ;

Coffer, Paul J. ;

Rudensky, Alexander Y. .

NATURE, 2013, 504 (7480) :451-+

[4] Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells [J].

Atarashi, Koji ;

Tanoue, Takeshi ;

Ando, Minoru ;

Kamada, Nobuhiko ;

Nagano, Yuji ;

Narushima, Seiko ;

Suda, Wataru ;

Imaoka, Akemi ;

Setoyama, Hiromi ;

Nagamori, Takashi ;

Ishikawa, Eiji ;

Shima, Tatsuichiro ;

Hara, Taeko ;

Kado, Shoichi ;

Jinnohara, Toshi ;

Ohno, Hiroshi ;

Kondo, Takashi ;

Toyooka, Kiminori ;

Watanabe, Eiichiro ;

Yokoyama, Shin-ichiro ;

Tokoro, Shunji ;

Mori, Hiroshi ;

Noguchi, Yurika ;

Morita, Hidetoshi ;

Ivanov, Ivaylo I. ;

Sugiyama, Tsuyoshi ;

Nunez, Gabriel ;

Camp, J. Gray ;

Hattori, Masahira ;

Umesaki, Yoshinori ;

Honda, Kenya .

CELL, 2015, 163 (02) :367-380

[5] Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors [J].

Colosimo, Dominic A. ;

Kohn, Jeffrey A. ;

Luo, Peter M. ;

Piscotta, Frank J. ;

Han, Sun M. ;

Pickard, Amanda J. ;

Rao, Arka ;

Cross, Justin R. ;

Cohen, Louis J. ;

Brady, Sean F. .

CELL HOST & MICROBE, 2019, 26 (02) :273-+

[6] Species-level functional profiling of metagenomes and metatranscriptomes [J].

Franzosa, Eric A. ;

McIver, Lauren J. ;

Rahnavard, Gholamali ;

Thompson, Luke R. ;

Schirmer, Melanie ;

Weingart, George ;

Lipson, Karen Schwarzberg ;

Knight, Rob ;

Caporaso, J. Gregory ;

Segata, Nicola ;

Huttenhower, Curtis .

NATURE METHODS, 2018, 15 (11) :962-+

[7] Microbial metabolite sensor GPR43 controls severity of experimental GVHD [J].

Fujiwara, Hideaki ;

Docampo, Melissa D. ;

Riwes, Mary ;

Peltier, Daniel ;

Toubai, Tomomi ;

Henig, Israel ;

Wu, S. Julia ;

Kim, Stephanie ;

Taylor, Austin ;

Brabbs, Stuart ;

Liu, Chen ;

Zajac, Cynthia ;

Oravecz-Wilson, Katherine ;

Sun, Yaping ;

Nunez, Gabriel ;

Levine, John E. ;

van den Brink, Marcel R. M. ;

Ferrara, James L. M. ;

Reddy, Pavan .

NATURE COMMUNICATIONS, 2018, 9

[8] Immune checkpoint inhibitors in urothelial cancer: recent updates and future outlook [J].

Gopalakrishnan, Dharmesh ;

Koshkin, Vadim S. ;

Ornstein, Moshe C. ;

Papatsoris, Athanasios ;

Grivas, Petros .

THERAPEUTICS AND CLINICAL RISK MANAGEMENT, 2018, 14 :1019-1040

[9] Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT [J].

Haak, Bastiaan W. ;

Littmann, Eric R. ;

Chaubard, Jean-Luc ;

Pickard, Amanda J. ;

Fontana, Emily ;

Adhi, Fatima ;

Gyaltshen, Yangtsho ;

Ling, Lilan ;

Morjaria, Sejal M. ;

Peled, Jonathan U. ;

van den Brink, Marcel R. ;

Geyer, Alexander I. ;

Cross, Justin R. ;

Pamer, Eric G. ;

Taur, Ying .

BLOOD, 2018, 131 (26) :2978-2986

[10] Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma [J].

Hill, Geoffrey R. ;

Olver, Stuart D. ;

Kuns, Rachel D. ;

Varelias, Antiopi ;

Raffelt, Neil C. ;

Don, Alistair L. ;

Markey, Kate A. ;

Wilson, Yana A. ;

Smyth, Mark J. ;

Iwakura, Yoichiro ;

Tocker, Joel ;

Clouston, Andrew D. ;

MacDonald, Kelli P. A. .

BLOOD, 2010, 116 (05) :819-828

← 1 2 3 4 →