Abstract

The microbiota, comprising bacteria, fungi, and viruses residing within our bodies, functions as a key modulator in host health and states, including immune responses. Studies have linked microbiota and microbiota-derived metabolites to immune cell functions. In this review, we probe the complex relationship between the human microbiota and clinical outcomes of cellular therapies that leverage immune cells to fight various cancers. With a particular emphasis on hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy, we explore the potential mechanisms underpinning this interaction. We also highlight the interventional applications of the microbiota in cellular therapy while outlining future research directions in the field.

1.
Klein
HG
. Transfusion medicine. In:
Winslow
R.
, eds.
Blood Substitutes
. 1st ed..
Elsevier Ltd
;
2006
:
17
-
33
.
2.
Henig
I
,
Zuckerman
T
.
Hematopoietic stem cell transplantation—50 years of evolution and future perspectives
.
Rambam Maimonides Med J
.
2014
;
5
(
4
):
e0028
.
3.
Rosenberg
SA
,
Packard
BS
,
Aebersold
PM
, et al
.
Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma
.
N Engl J Med
.
1988
;
319
(
25
):
1676
-
1680
.
4.
Rosenberg
SA
,
Yannelli
JR
,
Yang
JC
, et al
.
Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2
.
J Natl Cancer Inst
.
1994
;
86
(
15
):
1159
-
1166
.
5.
Lin
X
,
Lee
S
,
Sharma
P
,
George
B
,
Scott
J
.
Summary of US Food and Drug Administration chimeric antigen receptor (CAR) T-cell biologics license application approvals from a statistical perspective
.
J Clin Orthod
.
2022
;
40
(
30
):
3501
-
3509
.
6.
Mullard
A
.
FDA approval of Immunocore’s first-in-class TCR therapeutic broadens depth of the T cell engager platform
.
Nat Rev Drug Discov
.
2022
;
21
(
3
):
170
.
7.
Zeiser
R
,
Blazar
BR
.
Acute graft-versus-host disease–biologic process, prevention, and therapy
.
N Engl J Med
.
2017
;
377
(
22
):
2167
-
2179
.
8.
Zeiser
R
,
Blazar
BR
.
Pathophysiology of chronic graft-versus-host disease and therapeutic targets
.
N Engl J Med
.
2017
;
377
(
26
):
2565
-
2579
.
9.
Dougan
M
,
Luoma
AM
,
Dougan
SK
,
Wucherpfennig
KW
.
Understanding and treating the inflammatory adverse events of cancer immunotherapy
.
Cell
.
2021
;
184
(
6
):
1575
-
1588
.
10.
Fan
Y
,
Pedersen
O
.
Gut microbiota in human metabolic health and disease
.
Nat Rev Microbiol
.
2021
;
19
(
1
):
55
-
71
.
11.
Sender
R
,
Fuchs
S
,
Milo
R
.
Revised estimates for the number of human and bacteria cells in the body
.
PLoS Biol
.
2016
;
14
(
8
):
e1002533
.
12.
Schroeder
BO
,
Bäckhed
F
.
Signals from the gut microbiota to distant organs in physiology and disease
.
Nat Med
.
2016
;
22
(
10
):
1079
-
1089
.
13.
Dickinson
AM
,
Norden
J
,
Li
S
, et al
.
Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia
.
Front Immunol
.
2017
;
8
:
496
-
511
.
14.
Taur
Y
,
Xavier
JB
,
Lipuma
L
, et al
.
Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation
.
Clin Infect Dis
.
2012
;
55
(
7
):
905
-
914
.
15.
Morjaria
S
,
Schluter
J
,
Taylor
BP
, et al
.
Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation
.
Infect Immun
.
2019
;
87
(
9
):
e00206-19
.
16.
Khan
N
,
Lindner
S
,
Gomes
ALC
, et al
.
Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study
.
Blood
.
2021
;
137
(
11
):
1527
-
1537
.
17.
Miltiadous
O
,
Waters
NR
,
Andrlová
H
, et al
.
Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant
.
Blood
.
2022
;
139
(
18
):
2758
-
2769
.
18.
Masetti
R
,
Leardini
D
,
Muratore
E
, et al
.
Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children
.
Blood
.
2023
;
142
(
16
):
1387
-
1398
.
19.
Peled
JU
,
Gomes
ALC
,
Devlin
SM
, et al
.
Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation
.
N Engl J Med
.
2020
;
382
(
9
):
822
-
834
.
20.
Taur
Y
,
Jenq
RR
,
Perales
M-A
, et al
.
The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation
.
Blood
.
2014
;
124
(
7
):
1174
-
1182
.
21.
D’Angelo
C
,
Sudakaran
S
,
Asimakopoulos
F
, et al
.
Perturbation of the gut microbiome and association with outcomes following autologous stem cell transplantation in patients with multiple myeloma
.
Leuk Lymphoma
.
2023
;
64
(
1
):
87
-
97
.
22.
Montassier
E
,
Al-Ghalith
GA
,
Ward
T
, et al
.
Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection
.
Genome Med
.
2016
;
8
(
1
):
49
-
59
.
23.
Yin
G
,
Guo
Y
,
Ding
Q
, et al
.
Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection
.
J Transl Med
.
2023
;
21
(
1
):
230
-
244
.
24.
Golob
JL
,
Pergam
SA
,
Srinivasan
S
, et al
.
Stool microbiota at neutrophil recovery is predictive for severe acute graft vs host disease after hematopoietic cell transplantation
.
Clin Infect Dis
.
2017
;
65
(
12
):
1984
-
1991
.
25.
El Jurdi
N
,
Holtan
SG
,
Hoeschen
A
, et al
.
Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease
.
Br J Haematol
.
2023
;
203
(
2
):
288
-
294
.
26.
El Jurdi
N
,
Filali-Mouhim
A
,
Salem
I
, et al
.
Gastrointestinal microbiome and mycobiome changes during autologous transplantation for multiple myeloma: results of a prospective pilot study
.
Biol Blood Marrow Transplant
.
2019
;
25
(
8
):
1511
-
1519
.
27.
Harris
B
,
Morjaria
SM
,
Littmann
ER
, et al
.
Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation
.
Am J Respir Crit Care Med
.
2016
;
194
(
4
):
450
-
463
.
28.
Scordo
M
,
Shah
GL
,
Adintori
PA
, et al
.
A prospective study of dysgeusia and related symptoms in patients with multiple myeloma after autologous hematopoietic cell transplantation
.
Cancer
.
2022
;
128
(
21
):
3850
-
3859
.
29.
Andrlová
H
,
Miltiadous
O
,
Kousa
AI
, et al
.
MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT
.
Sci Transl Med
.
2022
;
14
(
646
):
eabj2829
.
30.
Hu
Y
,
Li
J
,
Ni
F
, et al
.
CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies
.
Nat Commun
.
2022
;
13
(
1
):
5313
-
5326
.
31.
Staffas
A
,
Burgos da Silva
M
,
Slingerland
AE
, et al
.
Nutritional support from the intestinal microbiota improves hematopoietic reconstitution after bone marrow transplantation in mice
.
Cell Host Microbe
.
2018
;
23
(
4
):
447
-
457.e4
.
32.
Seike
K
,
Kiledal
A
,
Fujiwara
H
, et al
.
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
.
Immunity
.
2023
;
56
(
2
):
353
-
368.e6
.
33.
Sofi
MH
,
Wu
Y
,
Ticer
T
, et al
.
A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD
.
JCI Insight
.
2021
;
6
(
3
):
e136841
.
34.
Pan
P
,
Atkinson
SN
,
Taylor
B
, et al
.
Retinoic acid signaling modulates recipient gut barrier integrity and microbiota after allogeneic hematopoietic stem cell transplantation in mice
.
Front Immunol
.
2021
;
12
:
749002
.
35.
Bowerman
KL
,
Varelias
A
,
Lachner
N
,
Kuns
RD
,
Hill
GR
,
Hugenholtz
P
.
Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice
.
Gut Microb
.
2020
;
11
(
4
):
754
-
770
.
36.
Uribe-Herranz
M
,
Beghi
S
,
Ruella
M
, et al
.
Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy
.
Mol Ther
.
2023
;
31
(
3
):
686
-
700
.
37.
Peled
JU
,
Devlin
SM
,
Staffas
A
, et al
.
Intestinal microbiota and relapse after hematopoietic-cell transplantation
.
J Clin Orthod
.
2017
;
35
(
15
):
1650
-
1659
.
38.
Burgos da Silva
M
,
Ponce
DM
,
Dai
A
, et al
.
Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease
.
Blood
.
2022
;
140
(
22
):
2385
-
2397
.
39.
Markey
KA
,
Schluter
J
,
Gomes
ALC
, et al
.
The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD
.
Blood
.
2020
;
136
(
1
):
130
-
136
.
40.
Stein-Thoeringer
CK
,
Nichols
KB
,
Lazrak
A
, et al
.
Lactose drives enterococcus expansion to promote graft-versus-host disease
.
Science
.
2019
;
366
(
6469
):
1143
-
1149
.
41.
Schluter
J
,
Peled
JU
,
Taylor
BP
, et al
.
The gut microbiota is associated with immune cell dynamics in humans
.
Nature
.
2020
;
588
(
7837
):
303
-
307
.
42.
Vallet
N
,
Salmona
M
,
Malet-Villemagne
J
, et al
.
Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses
.
Cell Host Microbe
.
2023
;
31
(
8
):
1386
-
1403.e6
.
43.
Shono
Y
,
van den Brink
MRM
.
Gut microbiota injury in allogeneic haematopoietic stem cell transplantation
.
Nat Rev Cancer
.
2018
;
18
(
5
):
283
-
295
.
44.
Nguyen
CL
,
Docampo
MD
,
van den Brink
MR
,
Markey
KA
.
The role of the intestinal microbiota in allogeneic HCT: clinical associations and preclinical mechanisms
.
Curr Opin Genet Dev
.
2021
;
66
:
25
-
35
.
45.
Shouval
R
,
Waters
NR
,
Gomes
ALC
, et al
.
Conditioning regimens are associated with distinct patterns of microbiota injury in allogeneic hematopoietic cell transplantation
.
Clin Cancer Res
.
2023
;
29
(
1
):
165
-
173
.
46.
Liao
C
,
Taylor
BP
,
Ceccarani
C
, et al
.
Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients
.
Sci Data
.
2021
;
8
(
1
):
71
-
82
.
47.
Routy
B
,
Letendre
C
,
Enot
D
, et al
.
The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation
.
OncoImmunology
.
2017
;
6
(
1
):
e1258506
.
48.
Tanaka
JS
,
Young
RR
,
Heston
SM
, et al
.
Anaerobic antibiotics and the risk of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
.
Biol Blood Marrow Transplant
.
2020
;
26
(
11
):
2053
-
2060
.
49.
Shono
Y
,
Docampo
MD
,
Peled
JU
, et al
.
Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice
.
Sci Transl Med
.
2016
;
8
(
339
):
339ra71
.
50.
Weber
D
,
Jenq
RR
,
Peled
JU
, et al
.
Microbiota disruption induced by early use of broad-spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation
.
Biol Blood Marrow Transplant
.
2017
;
23
(
5
):
845
-
852
.
51.
Vallet
N
,
Le Grand
S
,
Bondeelle
L
, et al
.
Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation
.
Blood
.
2022
;
140
(
23
):
2500
-
2513
.
52.
Ogimi
C
,
Krantz
EM
,
Golob
JL
, et al
.
Exposure to antibiotics with anaerobic activity before respiratory viral infection is associated with respiratory disease progression after hematopoietic cell transplant
.
Bone Marrow Transplant
.
2022
;
57
(
12
):
1765
-
1773
.
53.
Zhang
S
,
Shanley
R
,
Weisdorf
DJ
,
Rashidi
A
.
Vancomycin use and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation
.
Blood Adv
.
2020
;
4
(
12
):
2640
-
2643
.
54.
Haak
BW
,
Littmann
ER
,
Chaubard
J-L
, et al
.
Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT
.
Blood
.
2018
;
131
(
26
):
2978
-
2986
.
55.
Satlin
MJ
,
Chen
L
,
Douglass
C
, et al
.
Colonization with fluoroquinolone-resistant enterobacterales decreases the effectiveness of fluoroquinolone prophylaxis in hematopoietic cell transplant recipients
.
Clin Infect Dis
.
2021
;
73
(
7
):
1257
-
1265
.
56.
Vossen
JM
,
Guiot
HFL
,
Lankester
AC
, et al
.
Complete suppression of the gut microbiome prevents acute graft-versus-host disease following allogeneic bone marrow transplantation
.
PLoS One
.
2014
;
9
(
9
):
e105706
.
57.
Rashidi
A
,
Gao
F
,
Fredricks
DN
, et al
.
Analysis of antibiotic exposure and development of acute graft-vs-host disease following allogeneic hematopoietic cell transplantation
.
JAMA Netw Open
.
2023
;
6
(
6
):
e2317188
.
58.
Elgarten
CW
,
Li
Y
,
Getz
KD
, et al
.
Broad-spectrum antibiotics and risk of graft-versus-host disease in pediatric patients undergoing transplantation for acute leukemia: association of carbapenem use with the risk of acute graft-versus-host disease
.
Transplant Cell Ther
.
2021
;
27
(
2
):
177.e1
-
177.e8
.
59.
Hayase
E
,
Hayase
T
,
Jamal
MA
, et al
.
Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease
.
Cell
.
2022
;
185
(
20
):
3705
-
3719.e14
.
60.
Simms-Waldrip
TR
,
Sunkersett
G
,
Coughlin
LA
, et al
.
Antibiotic-induced depletion of anti-inflammatory clostridia is associated with the development of graft-versus-host disease in pediatric stem cell transplantation patients
.
Biol Blood Marrow Transplant
.
2017
;
23
(
5
):
820
-
829
.
61.
Solano
C
,
Gutierrez
A
,
Martinez
F
, et al
.
Prophylaxis of early bacterial infections after autologous peripheral blood stem cell transplantation (PBSCT): a matched-pair study comparing oral fluoroquinolones and intravenous piperacillin–tazobactam
.
Bone Marrow Transplant
.
2005
;
36
(
1
):
59
-
65
.
62.
Eleutherakis-Papaiakovou
E
,
Kostis
E
,
Migkou
M
, et al
.
Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial
.
Am J Hematol
.
2010
;
85
(
11
):
863
-
867
.
63.
Beelen
DW
,
Elmaagacli
A
,
Müller
K-D
,
Hirche
H
,
Schaefer
UW
.
Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial
.
Blood
.
1999
;
93
(
10
):
3267
-
3275
.
64.
Severyn
CJ
,
Siranosian
BA
,
Kong
ST-J
, et al
.
Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation
.
JCI Insight
.
2022
;
7
(
7
):
e154344
.
65.
Bansal
R
,
Park
H
,
Taborda
CC
, et al
.
Antibiotic exposure, not alloreactivity, is the major driver of microbiome changes in hematopoietic cell transplantation
.
Transplant Cell Ther
.
2022
;
28
(
3
):
135
-
144
.
66.
Baydoun
M
,
Otrock
ZK
,
Okaily
S
, et al
.
Prophylactic administration of doxycycline reduces central venous catheter infections in patients undergoing hematopoietic cell transplantation
.
Mediterr J Hematol Infect Dis
.
2013
;
5
(
1
):
e2013015
.
67.
Pérez-Simón
JA
,
García-Escobar
I
,
Martinez
J
, et al
.
Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation
.
Bone Marrow Transplant
.
2004
;
33
(
2
):
183
-
187
.
68.
Smith
M
,
Dai
A
,
Ghilardi
G
, et al
.
Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy
.
Nat Med
.
2022
;
28
(
4
):
713
-
723
.
69.
Stein-Thoeringer
CK
,
Saini
NY
,
Zamir
E
, et al
.
A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy
.
Nat Med
.
2023
;
29
(
4
):
906
-
916
.
70.
Zhai
B
,
Ola
M
,
Rolling
T
, et al
.
High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis
.
Nat Med
.
2020
;
26
(
1
):
59
-
64
.
71.
Rolling
T
,
Zhai
B
,
Gjonbalaj
M
, et al
.
Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species
.
Nat Microbiol
.
2021
;
6
(
12
):
1505
-
1515
.
72.
Naghavian
R
,
Faigle
W
,
Oldrati
P
, et al
.
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma
.
Nature
.
2023
;
617
(
7962
):
807
-
817
.
73.
Daillère
R
,
Vétizou
M
,
Waldschmitt
N
, et al
.
Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects
.
Immunity
.
2016
;
45
(
4
):
931
-
943
.
74.
Hamada
T
,
Zhang
X
,
Mima
K
, et al
.
Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status
.
Cancer Immunol Res
.
2018
;
6
(
11
):
1327
-
1336
.
75.
Yu
Q
,
Newsome
RC
,
Beveridge
M
, et al
.
Intestinal microbiota modulates pancreatic carcinogenesis through intratumoral natural killer cells
.
Gut Microb
.
2022
;
14
(
1
):
2112881
.
76.
Lam
KC
,
Araya
RE
,
Huang
A
, et al
.
Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment
.
Cell
.
2021
;
184
(
21
):
5338
-
5356.e21
.
77.
Shafer
P
,
Kelly
LM
,
Hoyos
V
.
Cancer therapy with TCR-engineered T cells: current strategies, challenges, and prospects
.
Front Immunol
.
2022
;
13
:
835762
.
78.
Viaud
S
,
Saccheri
F
,
Mignot
G
, et al
.
The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide
.
Science
.
2013
;
342
(
6161
):
971
-
976
.
79.
Kuczma
MP
,
Ding
Z-C
,
Li
T
, et al
.
The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells
.
Oncotarget
.
2017
;
8
(
67
):
111931
-
111942
.
80.
Bauer
MA
,
Kainz
K
,
Carmona-Gutierrez
D
,
Madeo
F
.
Microbial wars: competition in ecological niches and within the microbiome
.
Microb Cell
.
2018
;
5
(
5
):
215
-
219
.
81.
Cerboni
S
,
Jeremiah
N
,
Gentili
M
, et al
.
Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes
.
J Exp Med
.
2017
;
214
(
6
):
1769
-
1785
.
82.
Curran
E
,
Chen
X
,
Corrales
L
, et al
.
STING pathway activation stimulates potent immunity against acute myeloid leukemia
.
Cell Rep
.
2016
;
15
(
11
):
2357
-
2366
.
83.
Nicolai
CJ
,
Wolf
N
,
Chang
I-C
, et al
.
NK cells mediate clearance of CD8+ T cell–resistant tumors in response to STING agonists
.
Sci Immunol
.
2020
;
5
(
45
):
eaaz2738
.
84.
Luu
M
,
Riester
Z
,
Baldrich
A
, et al
.
Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
.
Nat Commun
.
2021
;
12
(
1
):
4077
-
4088
.
85.
Luu
M
,
Weigand
K
,
Wedi
F
, et al
.
Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate
.
Sci Rep
.
2018
;
8
(
1
):
14430
.
86.
Docampo
MD
,
da Silva
MB
,
Lazrak
A
, et al
.
Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109A induce less graft-versus-host disease
.
Blood
.
2022
;
139
(
15
):
2392
-
2405
.
87.
Tian
P
,
Yang
W
,
Guo
X
, et al
.
Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis
.
Nat Commun
.
2023
;
14
(
1
):
1710
-
1725
.
88.
Jia
D
,
Wang
Q
,
Qi
Y
, et al
.
Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer
.
Cell
.
2024
;
187
(
7
):
1651
-
1665.e21
.
89.
Lindner
S
,
Miltiadous
O
,
Ramos
RJF
, et al
.
Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease
.
Nat Microbiol
.
2024
;
9
(
3
):
614
-
630
.
90.
Haring
E
,
Uhl
FM
,
Andrieux
G
, et al
.
Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect
.
Haematologica
.
2021
;
106
(
8
):
2131
-
2146
.
91.
Ma
S
,
Wu
Q
,
Wu
W
, et al
.
Urolithin A Hijacks ERK1/2-ULK1 cascade to improve CD8+ T cell fitness for antitumor immunity
.
Adv Sci
.
2024
;
11
(
18
):
2310065
.
92.
Paulos
CM
,
Wrzesinski
C
,
Kaiser
Andrew
, et al
.
Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling
.
J Clin Invest
.
2007
;
117
(
8
):
2197
-
2204
.
93.
Zhang
Q
,
Zhao
Q
,
Li
T
, et al
.
Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8+ T cell immunity
.
Cell Metab
.
2023
;
35
(
6
):
943
-
960.e9
.
94.
Agliardi
G
,
Liuzzi
AR
,
Hotblack
A
, et al
.
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma
.
Nat Commun
.
2021
;
12
(
1
):
444
-
454
.
95.
Landoni
E
,
Woodcock
MG
,
Barragan
G
, et al
.
IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity
.
Nat Commun
.
2024
;
15
(
1
):
89
-
104
.
96.
Wang
H
,
Jiang
D
,
Liu
L
, et al
.
Spermidine promotes Nb CAR-T mediated cytotoxicity to lymphoma cells through elevating proliferation and memory
.
OTT
.
2022
;
15
:
1229
-
1243
.
97.
Denk
D
,
Petrocelli
V
,
Conche
C
, et al
.
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy
.
Immunity
.
2022
;
55
(
11
):
2059
-
2073.e8
.
98.
Klysz
DD
,
Fowler
C
,
Malipatlolla
M
, et al
.
Inosine induces stemness features in CAR-T cells and enhances potency
.
Cancer Cell
.
2024
;
42
(
2
):
266
-
282.e8
.
99.
Rafei
H
,
Jenq
RR
.
Microbiome-intestine cross talk during acute graft-versus-host disease
.
Blood
.
2020
;
136
(
4
):
401
-
409
.
100.
Schwab
L
,
Goroncy
L
,
Palaniyandi
S
, et al
.
Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage
.
Nat Med
.
2014
;
20
(
6
):
648
-
654
.
101.
Hossain
MS
,
Jaye
DL
,
Pollack
BP
, et al
.
Flagellin, a TLR5 agonist, reduces graft-versus-host disease in allogeneic hematopoietic stem cell transplantation recipients while enhancing antiviral immunity
.
J Immunol
.
2011
;
187
(
10
):
5130
-
5140
.
102.
Bader
CS
,
Jin
L
,
Levy
RB
.
STING and transplantation: can targeting this pathway improve outcomes?
.
Blood
.
2021
;
137
(
14
):
1871
-
1878
.
103.
Fischer
JC
,
Bscheider
M
,
Eisenkolb
G
, et al
.
RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury
.
Sci Transl Med
.
2017
;
9
(
386
):
eaag2513
.
104.
Fischer
JC
,
Bscheider
M
,
Göttert
S
, et al
.
Type I interferon signaling before hematopoietic stem cell transplantation lowers donor T cell activation via reduced allogenicity of recipient cells
.
Sci Rep
.
2019
;
9
(
1
):
14955
.
105.
Michonneau
D
,
Latis
E
,
Curis
E
, et al
.
Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites
.
Nat Commun
.
2019
;
10
(
1
):
5695
-
5709
.
106.
Romick-Rosendale
LE
,
Haslam
DB
,
Lane
A
, et al
.
Antibiotic exposure and reduced short chain fatty acid production after hematopoietic stem cell transplant
.
Biol Blood Marrow Transplant
.
2018
;
24
(
12
):
2418
-
2424
.
107.
Mathewson
ND
,
Jenq
R
,
Mathew
AV
, et al
.
Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease
.
Nat Immunol
.
2016
;
17
(
5
):
505
-
513
.
108.
Zheng
Y
,
Josefowicz
S
,
Chaudhry
A
,
Peng
XP
,
Forbush
K
,
Rudensky
AY
.
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
.
Nature
.
2010
;
463
(
7282
):
808
-
812
.
109.
Fujiwara
H
,
Docampo
MD
,
Riwes
M
, et al
.
Microbial metabolite sensor GPR43 controls severity of experimental GVHD
.
Nat Commun
.
2018
;
9
(
1
):
3674
-
3688
.
110.
Smith
PM
,
Howitt
MR
,
Panikov
N
, et al
.
The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis
.
Science
.
2013
;
341
(
6145
):
569
-
573
.
111.
Swimm
A
,
Giver
CR
,
DeFilipp
Z
, et al
.
Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease
.
Blood
.
2018
;
132
(
23
):
2506
-
2519
.
112.
Henry
CJ
,
Ornelles
DA
,
Mitchell
LM
,
Brzoza-Lewis
KL
,
Hiltbold
EM
.
IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17
.
J Immunol
.
2008
;
181
(
12
):
8576
-
8584
.
113.
Cong
J
,
Liu
P
,
Han
Z
, et al
.
Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions
.
Immunity
.
2024
;
57
(
4
):
876
-
889.e11
.
114.
Hang
S
,
Paik
D
,
Yao
L
, et al
.
Bile acid metabolites control TH17 and Treg cell differentiation
.
Nature
.
2019
;
576
(
7785
):
143
-
148
.
115.
Campbell
C
,
McKenney
PT
,
Konstantinovsky
D
, et al
.
Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells
.
Nature
.
2020
;
581
(
7809
):
475
-
479
.
116.
Tofalo
R
,
Cocchi
S
,
Suzzi
G
.
Polyamines and gut microbiota
.
Front Nutr
.
2019
;
6
:
16
.
117.
Shouval
R
,
Eshel
A
,
Dubovski
B
, et al
.
Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation
.
Blood Adv
.
2020
;
4
(
13
):
2912
-
2917
.
118.
Rao
JN
,
Xiao
L
,
Wang
J-Y
.
Polyamines in gut epithelial renewal and barrier function
.
Physiology
.
2020
;
35
(
5
):
328
-
337
.
119.
Fahrmann
JF
,
Saini
NY
,
Chia-Chi
C
, et al
.
A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma
.
Cell Rep Med
.
2022
;
3
(
11
):
100720
.
120.
Al-Habsi
M
,
Chamoto
K
,
Matsumoto
K
, et al
.
Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice
.
Science
.
2022
;
378
(
6618
):
eabj3510
.
121.
Mager
LF
,
Burkhard
R
,
Pett
N
, et al
.
Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
.
Science
.
2020
;
369
(
6510
):
1481
-
1489
.
122.
DeFilipp
Z
,
Peled
JU
,
Li
S
, et al
.
Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity
.
Blood Adv
.
2018
;
2
(
7
):
745
-
753
.
123.
Rashidi
A
,
Ebadi
M
,
Rehman
TU
, et al
.
Randomized double-blind phase II trial of fecal microbiota transplantation versus placebo in allogeneic hematopoietic cell transplantation and AML
.
J Clin Orthod
.
2023
;
41
(
34
):
5306
-
5319
.
124.
Neemann
K
,
Eichele
DD
,
Smith
PW
,
Bociek
R
,
Akhtari
M
,
Freifeld
A
.
Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient
.
Transpl Infect Dis
.
2012
;
14
(
6
):
E161
-
E165
.
125.
de Castro
CG
,
Ganc
AJ
,
Ganc
RL
,
Petrolli
MS
,
Hamerschlack
N
.
Fecal microbiota transplant after hematopoietic SCT: report of a successful case
.
Bone Marrow Transplant
.
2015
;
50
(
1
):
145
.
126.
Battipaglia
G
,
Malard
F
,
Rubio
MT
, et al
.
Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria
.
Haematologica
.
2019
;
104
(
8
):
1682
-
1688
.
127.
Kakihana
K
,
Fujioka
Y
,
Suda
W
, et al
.
Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut
.
Blood
.
2016
;
128
(
16
):
2083
-
2088
.
128.
DeFilipp
Z
,
Damania
AV
,
Kim
HT
, et al
.
Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract
.
Blood Advances
.
2024
;
8
(
9
):
2074
-
2084
.
129.
Rashidi
A
,
Ebadi
M
,
Rehman
TU
, et al
.
Potential of fecal microbiota transplantation to prevent acute GVHD: analysis from a phase II trial
.
Clin Cancer Res
.
2023
;
29
(
23
):
4920
-
4929
.
130.
Rizvi
ZA
,
Dalal
R
,
Sadhu
S
, et al
.
High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity
.
Sci Adv
.
2021
;
7
(
37
):
eabg5016
.
131.
Riwes
MM
,
Golob
JL
,
Magenau
J
, et al
.
Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation
.
Nat Med
.
2023
;
29
(
11
):
2805
-
2813
.
132.
Nguyen
CL
,
Markey
KA
,
Miltiadous
O
, et al
.
High-resolution analyses of associations between medications, microbiome, and mortality in cancer patients
.
Cell
.
2023
;
186
(
12
):
2705
-
2718.e17
.
133.
Weber
D
,
Oefner
PJ
,
Dettmer
K
, et al
.
Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation
.
Bone Marrow Transplant
.
2016
;
51
(
8
):
1087
-
1092
.
134.
Weber
D
,
Hiergeist
A
,
Weber
M
, et al
.
Restrictive versus permissive use of broad-spectrum antibiotics in patients receiving allogeneic stem cell transplantation and with early fever due to cytokine release syndrome: evidence for beneficial microbiota protection without increase in infectious complications
.
Clin Infect Dis
.
2023
;
77
(
10
):
1432
-
1439
.
135.
Fernandez Sanchez
J
,
Maknojia
AA
,
King
KY
.
Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease
.
Blood
.
2024
;
143
(
17
):
1689
-
1701
.
136.
Maghini
DG
,
Dvorak
M
,
Dahlen
A
, et al
.
Quantifying bias introduced by sample collection in relative and absolute microbiome measurements
.
Nat Biotechnol
.
2024
;
42
(
2
):
328
-
338
.
137.
Duscha
A
,
Gisevius
B
,
Hirschberg
S
, et al
.
Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism
.
Cell
.
2020
;
180
(
6
):
1067
-
1080.e16
.
138.
Rangan
P
,
Mondino
A
.
Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy
.
J Immunother Cancer
.
2022
;
10
(
7
):
e004147
.
139.
Gabrielli
G
,
Shouval
R
,
Ghilardi
G
,
van den Brink
M
,
Ruella
M
.
Harnessing the gut microbiota to potentiate the efficacy of CAR T cell therapy
.
HemaSphere
.
2023
;
7
(
9
):
e950
.
You do not currently have access to this content.
Sign in via your Institution