Dynamics in Circulating Immune Cell Subsets After Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

INTRODUCTION: 

Fecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial.

METHODS: 

Thirty-five patients with rCDI were randomized to vancomycin and FMT (n = 20) or vancomycin alone (n = 15). Blood samples were drawn before (wk0) and 1 week (wk1) after treatment. In 3 additional patients, blood samples were drawn before and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO⁺integrinβ7⁺) and effector (CD45RO^-integrinβ7⁺) T cells were analyzed by flow cytometry.

RESULTS: 

FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid T regulatory cells dynamics. Natural killer T (NKT) cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in nonclassical monocytes and a shift in gut-homing memory to effector cells at wk1.

DISCUSSION: 

In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. T regulatory cells and NKT cells seemed responsive and should be further studied. Cure of Clostridioides difficile infection may be associated with an increase in circulating gut-homing T cells.