Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose pa-tients 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. Histo-logically 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.

Automated summary

Immune checkpoint inhibitors (ICIs) are effective in treating advanced malignancies but can also lead to immune-related adverse events like immune-mediated colitis (IMC). Fecal microbiota transplantation (FMT) may be a beneficial treatment for IMC due to its ability to manipulate microbial composition. In this study, 12 patients with refractory IMC underwent FMT, resulting in symptom improvement in 83% of patients and requiring repeat FMT in 25% of patients.