Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

Marina Burgos da Silva; Doris M. Ponce; Anqi Dai; Sean M. Devlin; Antonio L.C. Gomes; Gillian Moore; John Slingerland; Roni Shouval; Gabriel K. Armijo; Susan DeWolf; Teng Fei; Annelie Clurman; Emily Fontana; Luigi A. Amoretti; Roberta J. Wright; Hana Andrlova; Oriana Miltiadous; Miguel Angel Perales; Ying Taur; Jonathan U. Peled; Marcel R.M. van den Brink

doi:10.1182/blood.2021015352

Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

Marina Burgos da Silva, Doris M. Ponce, Anqi Dai, Sean M. Devlin, Antonio L.C. Gomes, Gillian Moore, John Slingerland, Roni Shouval, Gabriel K. Armijo, Susan DeWolf, Teng Fei, Annelie Clurman, Emily Fontana, Luigi A. Amoretti, Roberta J. Wright, Hana Andrlova, Oriana Miltiadous, Miguel Angel Perales, Ying Taur, Jonathan U. PeledMarcel R.M. van den Brink

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Abstract

Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

Original language	English
Pages (from-to)	2385-2397
Number of pages	13
Journal	Blood
Volume	140
Issue number	22
DOIs	https://doi.org/10.1182/blood.2021015352
State	Published - 1 Dec 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The American Society of Hematology

Funding

This work was supported in part by the MSK Internal Diversity Enhancement Award (IDEA); National Institutes of Health, National Cancer Institute award numbers R01-CA228358 , R01-CA228308 , P30 CA008748 MSK Cancer Center Core Grant and P01-CA023766 ; National Heart, Lung, and Blood Institute award numbers R01-HL123340 , R01-HL147584 , and K08HL143189 ; National Institute of Aging award number P01-AG052359 ; Starr Cancer Consortium ; and Tri Institutional Stem Cell Initiative . Additional funding was received from the Lymphoma Foundation , The Susan and Peter Solomon Divisional Genomics Program , Cycle for Survival , MSKCC Cancer Systems Immunology Pilot Grant, Empire Clinical Research Investigator Program , the Society for MSK , the Staff Foundation , the American Society for Transplantation and Cellular Therapy, MSKCC Leukemia SPORE Career Enhancement Program , and the Parker Institute for Cancer Immunotherapy .

Funders	Funder number
Society for MSK
Staff Foundation
Starr Cancer Consortium
National Institutes of Health
National Institute on Aging	P01-AG052359
National Heart, Lung, and Blood Institute	K08HL143189, R01-HL123340, R01-HL147584
National Cancer Institute	P01-CA023766, R01-CA228308, P30 CA008748, R01-CA228358
Memorial Sloan-Kettering Cancer Center
Parker Institute for Cancer Immunotherapy
American Society for Transplantation and Cellular Therapy
Cycle for Survival

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10.1182/blood.2021015352

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Burgos da Silva, M., Ponce, D. M., Dai, A., M. Devlin, S., Gomes, A. L. C., Moore, G., Slingerland, J., Shouval, R., Armijo, G. K., DeWolf, S., Fei, T., Clurman, A., Fontana, E., Amoretti, L. A., Wright, R. J., Andrlova, H., Miltiadous, O., Perales, M. A., Taur, Y., ... van den Brink, M. R. M. (2022). Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease. Blood, 140(22), 2385-2397. https://doi.org/10.1182/blood.2021015352

@article{c8e7e1a10d4e44aead9deac4a23ea76d,

title = "Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease",

abstract = "Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.",

author = "{Burgos da Silva}, Marina and Ponce, {Doris M.} and Anqi Dai and {M. Devlin}, Sean and Gomes, {Antonio L.C.} and Gillian Moore and John Slingerland and Roni Shouval and Armijo, {Gabriel K.} and Susan DeWolf and Teng Fei and Annelie Clurman and Emily Fontana and Amoretti, {Luigi A.} and Wright, {Roberta J.} and Hana Andrlova and Oriana Miltiadous and Perales, {Miguel Angel} and Ying Taur and Peled, {Jonathan U.} and {van den Brink}, {Marcel R.M.}",

note = "Publisher Copyright: {\textcopyright} 2022 The American Society of Hematology",

year = "2022",

month = dec,

day = "1",

doi = "10.1182/blood.2021015352",

language = "אנגלית",

volume = "140",

pages = "2385--2397",

journal = "Blood",

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Burgos da Silva, M, Ponce, DM, Dai, A, M. Devlin, S, Gomes, ALC, Moore, G, Slingerland, J, Shouval, R, Armijo, GK, DeWolf, S, Fei, T, Clurman, A, Fontana, E, Amoretti, LA, Wright, RJ, Andrlova, H, Miltiadous, O, Perales, MA, Taur, Y, Peled, JU & van den Brink, MRM 2022, 'Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease', Blood, vol. 140, no. 22, pp. 2385-2397. https://doi.org/10.1182/blood.2021015352

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T1 - Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

AU - Burgos da Silva, Marina

AU - Ponce, Doris M.

AU - Dai, Anqi

AU - M. Devlin, Sean

AU - Gomes, Antonio L.C.

AU - Moore, Gillian

AU - Slingerland, John

AU - Shouval, Roni

AU - Armijo, Gabriel K.

AU - DeWolf, Susan

AU - Fei, Teng

AU - Clurman, Annelie

AU - Fontana, Emily

AU - Amoretti, Luigi A.

AU - Wright, Roberta J.

AU - Andrlova, Hana

AU - Miltiadous, Oriana

AU - Perales, Miguel Angel

AU - Taur, Ying

AU - Peled, Jonathan U.

AU - van den Brink, Marcel R.M.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

AB - Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

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Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

Abstract

Bibliographical note

Funding

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