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Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor–induced colitis
Open accessAbstract
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. 16 S 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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“The therapeutic mechanism of FMT appears multifaceted, involving not only the restoration of microbial richness but also immune modulation, as evidenced by reductions in CD8+ cytotoxic T cells and shifts in the Treg-to–cytotoxic T cell ratio within affected colonic tissues (Halsey et al., 2023).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Halsey et al., 2023
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Metadata
- Authors
- Halsey, T. M., Thomas, A. S., Hayase, T., Ma, W., Abu-Sbeih, H., Sun, B., Parra, E. R., Jiang, Z.-D., DuPont, H. L., Sanchez, C., El-Himri, R., Brown, A., Flores, I., McDaniel, L., Ortega Turrubiates, M., Hensel, M., Pham, D., Watowich, S. S., Hayase, E., Chang, C.-C., Jenq, R. R., & Wang, Y.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
- Center for Infectious Diseases, School of Public Health, University of Texas, Houston, TX 77054, USA.
- Kelsey Research Foundation (US)
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
- Middlebury College (US)
- Corresponding author
- Halsey, Taylor M.
- Thomas, Anusha S.
- Jenq, Robert R.
- Wang, Yinghong
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2023-06-14
- Volume
- 15
- Issue
- 700
- Pages
- eabq4006-eabq4006
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC10759507
- OpenAlex
- W4380590697
- Cited by
- 161
- References
- 66
- Citations by year
- 2026: 54 · 2025: 55 · 2024: 47 · 2023: 5
- FWCI
- 19.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science Translational Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (RP210042)
- Seres Therapeutics
- University of Texas MD Anderson Cancer Center
- National Heart, Lung, and Blood Institute (R01HL124112)
- National Cancer Institute (P30CA016672)
- Moonshot Research and Development Program
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- fecal microbiota transplantation, immune checkpoint inhibitors, immune-related colitis, immune-related adverse events, refractory colitis, gut microbiota, microbial signatures, Collinsella, Bifidobacterium, alpha diversity, CD8+ T cells, immunosuppressive therapy
- MeSH terms
- Fecal Microbiota Transplantation, Immune Checkpoint Inhibitors, Aged, Colitis, Feces, Female, Humans, Male, Middle Aged, RNA, Ribosomal, 16S
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