Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation
Open accessPublished version of a preprint
Abstract
Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second “salvage” FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recurrence of dysbiosis and clinical relapse after antibiotic use was subsequently corrected with a second FMT.
“The persistence of engraftment was supported by follow-up studies showing recurrence of dysbiosis and clinical relapse after antibiotic use, which was also subsequently corrected with a second FMT.233”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [233]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671 · see citing works
Self-citationGut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812 · see citing works
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J.-J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1910836 · Cited by 3,723 · see citing works
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., Andrews, E., Ajami, N. J., Bonham, K. S., Brislawn, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1237-9 · Cited by 3,143 · see citing works
Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., Minenza, E., Linardou, H., Burgers, S., Salman, P., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801946 · Cited by 3,063 · see citing works
Self-citationNivolumab plus ipilimumab in advanced non-small-cell lung cancer
Hellmann, M. D., Paz-Ares, L., Bernabe Caro, R., Zurawski, B., Kim, S.-W., Carcereny Costa, E., Park, K., Alexandru, A., Lupinacci, L., de la Mora Jimenez, E., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1910231 · Cited by 2,823 · see citing works
Self-citationMultivariable association discovery in population-scale meta-omics studies
Mallick, H., Rahnavard, A., McIver, L. J., Ma, S., Zhang, Y., Nguyen, L. H., Tickle, T. L., Weingart, G., Ren, B., Schwager, E. H., et al. (2021) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1009442 · Cited by 2,596 · see citing works
Population-level analysis of gut microbiome variation
Falony, G., Joossens, M., Vieira-Silva, S., Wang, J., Darzi, Y., Faust, K., Kurilshikov, A., Bonder, M. J., Valles-Colomer, M., Vandeputte, D., et al. (2016) · Science · doi:10.1126/science.aad3503 · Cited by 2,400 · see citing works
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648 · see citing works
Chaput, N., Lepage, P., Coutzac, C., Soularue, E., Le Roux, K., Monot, C., Boselli, L., Routier, E., Cassard, L., Collins, M., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx108 · Cited by 1,310 · see citing works
Enterotypes in the landscape of gut microbial community composition
Costea, P. I., Hildebrand, F., Arumugam, M., Bäckhed, F., Blaser, M. J., Bushman, F. D., de Vos, W. M., Ehrlich, S. D., Fraser, C. M., Hattori, M., et al. (2017) · Nature Microbiology · doi:10.1038/s41564-017-0072-8 · Cited by 1,138 · see citing works
Dubin, K., Callahan, M. K., Ren, B., Khanin, R., Viale, A., Ling, L., No, D., Gobourne, A., Littmann, E., Huttenhower, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms10391 · Cited by 987 · see citing works
Derosa, L., Hellmann, M. D., Spaziano, M., Halpenny, D., Fidelle, M., Rizvi, H., Long, N., Plodkowski, A. J., Arbour, K. C., Chaft, J. E., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy103 · Cited by 908 · see citing works
Self-citationMicrobiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation
Peled, J. U., Gomes, A. L. C., Devlin, S. M., Littmann, E. R., Taur, Y., Sung, A. D., Weber, D., Hashimoto, D., Slingerland, A. E., Slingerland, J. B., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1900623 · Cited by 765 · see citing works
Self-citationFecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis
Wang, Y., Wiesnoski, D. H., Helmink, B. A., Gopalakrishnan, V., Choi, K., DuPont, H. L., Jiang, Z.-D., Abu-Sbeih, H., Sanchez, C. A., Chang, C.-C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0238-9 · Cited by 740 · see citing works
Pinato, D. J., Howlett, S., Ottaviani, D., Urus, H., Patel, A., Mineo, T., Brock, C., Power, D., Hatcher, O., Falconer, A., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.2785 · Cited by 626 · see citing works
Faje, A. T., Lawrence, D., Flaherty, K., Freedman, C., Fadden, R., Rubin, K., Cohen, J., & Sullivan, R. J. (2018) · Cancer · doi:10.1002/cncr.31629 · Cited by 486 · see citing works
Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade
Andrews, M. C., Duong, C. P. M., Gopalakrishnan, V., Iebba, V., Chen, W.-S., Derosa, L., Khan, M. A. W., Cogdill, A. P., White, M. G., Wong, M. C., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01406-6 · Cited by 437 · see citing works
Self-citationGut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy
Smith, M., Dai, A., Ghilardi, G., Amelsberg, K. V., Devlin, S. M., Pajarillo, R., Slingerland, J. B., Beghi, S., Herrera, P. S., Giardina, P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01702-9 · Cited by 349 · see citing works
Self-citationHalsey, 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., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abq4006 · Cited by 161 · see citing works
Flagged first, then by citations
Research works printed but not linked: 7
- Khoja L, et al. , Tumour-and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol, 2017. 28(10): p. 2377-2385. [PubMed: 28945858]
- Wang DY, et al. , Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol, 2018. 4(12): p. 1721-1728. [PubMed: 30242316]
- Larkin J, et al. , Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine, 2019. 381(16): p. 1535-1546. [PubMed: 31562797]
- Brahmer JR, et al. , Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology, 2018. 36(17): p. 1714-1768. [PubMed: 29442540]
- Schluter J, et al. , The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia. bioRxiv, 2022: p. 2022.09.27.509746.
- Schluter J, et al. , The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia. bioRxiv, 2022: p. 2022.09.27.509746.
- Wang Y, et al. , Microbiome influencers of checkpoint blockade-associated toxicity. Journal of Experimental Medicine, 2023. 220(3).
Cited by
Sorted by citations
- Authors
- Elkrief, A., Waters, N. R., Smith, N., Dai, A., Slingerland, J., Aleynick, N., Febles, B., Gogia, P., Socci, N. D., Lumish, M., Giardina, P. A., Chaft, J. E., Eng, J., Motzer, R. J., Mendelsohn, R. B., Markey, K. A., Zhuang, M., Li, Y., Yang, Z., Hollmann, T. J., Rudin, C. M., van den Brink, M. R. M., Shia, J., DeWolf, S., Schoenfeld, A. J., Hellmann, M. D., Babady, N. E., Faleck, D. M., & Peled, J. U.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- 4Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
- University of Washington (US)
- Corresponding author
- Peled, Jonathan U.
- ORCID
- Elkrief, Arielle
- Waters, Nicholas R.
- Smith, Natalie
- Dai, Angel
- Slingerland, John
- Aleynick, Nathan
- Febles, Binita
- Gogia, Pooja
- Socci, Nicholas D.
- Lumish, Melissa
- Giardina, Paul A.
- Chaft, Jamie E.
- Eng, Juliana
- Motzer, Robert J.
- Mendelsohn, Robin B.
- Markey, Kate A.
- Zhuang, Mingqiang
- Li, Yanyun
- Yang, Zhifan
- Hollmann, Travis J.
- Rudin, Charles M.
- van den Brink, Marcel R.M.
- Shia, Jinru
- DeWolf, Susan
- Schoenfeld, Adam J.
- Hellmann, Matthew D.
- Babady, N. Esther
- Faleck, David M.
- Peled, Jonathan U.
- Venue
- Cancer Immunology Research
- Published
- 2023-12-15
- Volume
- 12
- Issue
- 3
- Pages
- 308-321
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC10932930
- OpenAlex
- W4389892676
- Cited by
- 48
- References
- 20
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 4
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL143189)
- 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 › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- immune-related colitis, immune checkpoint inhibitors, immune-related adverse events, fecal microbiota transplantation, gut dysbiosis, Proteobacteria, immunotherapy toxicity, refractory colitis, cancer immunotherapy
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Biological Products, Colitis, Humans, Prospective Studies, Treatment Outcome, Dysbiosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
