TY - JOUR
T1 - Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor–induced colitis
AU - Halsey, Taylor M.
AU - Thomas, Anusha S.
AU - Hayase, Tomo
AU - Ma, Weijie
AU - Abu-Sbeih, Hamzah
AU - Sun, Baohua
AU - Parra, Edwin Roger
AU - Jiang, Zhi Dong
AU - DuPont, Herbert L.
AU - Sanchez, Christopher
AU - El-Himri, Rawan
AU - Brown, Alexandria
AU - Flores, Ivonne
AU - McDaniel, Lauren
AU - Turrubiates, Miriam Ortega
AU - Hensel, Matthew
AU - Pham, Dung
AU - Watowich, Stephanie S.
AU - Hayase, Eiko
AU - Chang, Chia Chi
AU - Jenq, Robert R.
AU - Wang, Yinghong
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.
PY - 2023/6/14
Y1 - 2023/6/14
N2 - Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells, including CD8+ T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
AB - Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells, including CD8+ T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
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U2 - 10.1126/scitranslmed.abq4006
DO - 10.1126/scitranslmed.abq4006
M3 - Article
C2 - 37315113
AN - SCOPUS:85162041141
SN - 1946-6234
VL - 15
JO - Science translational medicine
JF - Science translational medicine
IS - 700
M1 - eabq4006
ER -