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Updated: Jun 1, 2026
Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-Deficient Mouse Model
Published on: April 6, 2022
Integration of donor microbiota following FMT correlates with anti-PD-1 response in melanoma
Jessica L Fessler1, Matthew R Olm2, Edgar G Engleman3,4
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:
Fecal microbiota transplantation (FMT) has shown promise in improving anti-PD-1 therapy in melanoma, but the underlying microbial features remain poorly defined. We performed a strain-resolved metagenomic meta-analysis across three independent FMT plus anti-PD-1 melanoma trials (n = 41). Across cohorts, therapeutic benefit was linked to successful integration of donor microbiota, rather than increased diversity or engraftment of specific species. Responders acquired more donor-derived strains, exhibited greater post-FMT similarity to their donor, and maintained a more stable microbiome. Following FMT, non-responders' microbiomes showed greater taxonomic instability, larger fluctuations in estimated microbial load, and increased abundance of pathogen-associated secretion system genes, whereas responders showed enrichment for microbial functions involved in community-level metabolism and communication. Finally, shifts in tumor-infiltrating immune profiles tracked with clinical outcomes and microbiome changes. Together these findings highlight that distinct patterns of microbiome restructuring, including stable community transitions and altered functional capacity, are associated with anti-PD-1 response following FMT.
Insights
Fecal microbiota transplantation (FMT) can improve anti-PD-1 therapy for melanoma by successfully integrating donor microbes. This leads to a more stable microbiome in responders, enhancing treatment effectiveness.
Area of Science:
- Immunology
- Microbiome Research
- Oncology
Background:
- Fecal microbiota transplantation (FMT) shows potential in enhancing anti-PD-1 immunotherapy for melanoma.
- The specific microbial changes driving this therapeutic benefit are not well understood.
Purpose of the Study:
- To investigate the microbial features associated with successful FMT and anti-PD-1 therapy response in melanoma patients.
- To identify key microbiome restructuring patterns linked to clinical outcomes.
Main Methods:
- Strain-resolved metagenomic meta-analysis of data from three independent FMT plus anti-PD-1 melanoma trials (n=41).
- Analysis of microbiome stability, donor strain integration, microbial load, and functional gene abundance.
- Correlation of microbiome changes with tumor-infiltrating immune profiles and clinical response.
Main Results:
- Therapeutic benefit correlated with successful donor microbiota integration and increased post-FMT similarity to the donor.
- Responders maintained a more stable microbiome, while non-responders exhibited instability and increased pathogen-associated genes.
- Responders showed enrichment in microbial functions related to community metabolism and communication.
- Changes in tumor-infiltrating immune cells mirrored microbiome shifts and clinical outcomes.
Conclusions:
- Successful FMT response in melanoma is characterized by stable microbiome restructuring and altered microbial functional capacity, not just species engraftment.
- Microbiome changes following FMT significantly impact anti-PD-1 therapy efficacy and are associated with immune system modulation.
