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
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
收藏
页码:130 / 136
页数:7
相关论文
共 33 条
[21]   Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study [J].
Pidala, Joseph ;
Vogelsang, Georgia ;
Martin, Paul ;
Chai, Xiaoyu ;
Storer, Barry ;
Pavletic, Steven ;
Weisdorf, Daniel J. ;
Jagasia, Madan ;
Cutler, Corey ;
Palmer, Jeanne ;
Jacobsohn, David ;
Arai, Sally ;
Lee, Stephanie J. .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (03) :451-458
[22]   The gut microbiota influences anticancer immunosurveillance and general health [J].
Routy, Bertrand ;
Gopalakrishnan, Vancheswaran ;
Daillere, Romain ;
Zitvogel, Laurence ;
Wargo, Jennifer A. ;
Kroemer, Guido .
NATURE REVIEWS CLINICAL ONCOLOGY, 2018, 15 (06) :382-396
[23]   Probabilistic programming in Python']Python using PyMC3 [J].
Salvatier, John ;
Wiecki, Thomas, V ;
Fonnesbeck, Christopher .
PEERJ COMPUTER SCIENCE, 2016, 2016 (04)
[24]   Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity [J].
Schirmer, Melanie ;
Smeekens, Sanne P. ;
Vlamakis, Hera ;
Jaeger, Martin ;
Oosting, Marije ;
Franzosa, Eric A. ;
ter Horst, Rob ;
Jansen, Trees ;
Jacobs, Liesbeth ;
Bonder, Marc Jan ;
Kurilshikov, Alexander ;
Fu, Jingyuan ;
Joosten, Leo A. B. ;
Zhernakova, Alexandra ;
Huttenhower, Curtis ;
Wijmenga, Cisca ;
Netea, Mihai G. ;
Xavier, Ramnik J. .
CELL, 2016, 167 (04) :1125-+
[25]  
Schluter J, 2019, GUT MICROBIOTA INFLU, DOI 10.1101/618256
[26]   Metagenomic biomarker discovery and explanation [J].
Segata, Nicola ;
Izard, Jacques ;
Waldron, Levi ;
Gevers, Dirk ;
Miropolsky, Larisa ;
Garrett, Wendy S. ;
Huttenhower, Curtis .
GENOME BIOLOGY, 2011, 12 (06)
[27]   Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis [J].
Shimizu, Jun ;
Kubota, Takao ;
Takada, Erika ;
Takai, Kenji ;
Fujiwara, Naruyoshi ;
Arimitsu, Nagisa ;
Murayama, Masanori A. ;
Ueda, Yuji ;
Wakisaka, Sueshige ;
Suzuki, Tomoko ;
Suzuki, Noboru .
PLOS ONE, 2018, 13 (09)
[28]   Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice [J].
Shono, Yusuke ;
Docampo, Melissa D. ;
Peled, Jonathan U. ;
Perobelli, Suelen M. ;
Velardi, Enrico ;
Tsai, Jennifer J. ;
Slingerland, Ann E. ;
Smith, Odette M. ;
Young, Lauren F. ;
Gupta, Jyotsna ;
Lieberman, Sophia R. ;
Jay, Hillary V. ;
Ahr, Katya F. ;
Rodriguez, Kori A. Porosnicu ;
Xu, Ke ;
Calarfiore, Marco ;
Poeck, Hendrik ;
Caballero, Silvia ;
Devlin, Sean M. ;
Rapaport, Franck ;
Dudakov, Jarrod A. ;
Hanash, Alan M. ;
Gyurkocza, Boglarka ;
Murphy, George F. ;
Gomes, Camilla ;
Liu, Chen ;
Moss, Eli L. ;
Falconer, Shannon B. ;
Bhatt, Ami S. ;
Taur, Ying ;
Pamer, Eric G. ;
van den Brink, Marcel R. M. ;
Jenq, Robert R. .
SCIENCE TRANSLATIONAL MEDICINE, 2016, 8 (339)
[29]   Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant [J].
Taur, Ying ;
Coyte, Katharine ;
Schluter, Jonas ;
Robilotti, Elizabeth ;
Figueroa, Cesar ;
Gjonbalaj, Mergim ;
Littmann, Eric R. ;
Ling, Lilan ;
Miller, Liza ;
Gyaltshen, Yangtsho ;
Fontana, Emily ;
Morjaria, Sejal ;
Gyurkocza, Boglarka ;
Perales, Miguel-Angel ;
Castro-Malaspina, Hugo ;
Tamari, Roni ;
Ponce, Doris ;
Koehne, Guenther ;
Barker, Juliet ;
Jakubowski, Ann ;
Papadopoulos, Esperanza ;
Dahi, Parastoo ;
Sauter, Craig ;
Shaffer, Brian ;
Young, James W. ;
Peled, Jonathan ;
Meagher, Richard C. ;
Jenq, Robert R. ;
van den Brink, Marcel R. M. ;
Giralt, Sergio A. ;
Pamer, Eric G. ;
Xavier, Joao B. .
SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (460)
[30]   The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation [J].
Taur, Ying ;
Jenq, Robert R. ;
Perales, Miguel-Angel ;
Littmann, Eric R. ;
Morjaria, Sejal ;
Ling, Lilan ;
No, Daniel ;
Gobourne, Asia ;
Viale, Agnes ;
Dahi, Parastoo B. ;
Ponce, Doris M. ;
Barker, Juliet N. ;
Giralt, Sergio ;
van den Brink, Marcel ;
Pamer, Eric G. .
BLOOD, 2014, 124 (07) :1174-1182