Fecal Microbiota Transplantation in Alzheimer’s Disease: A Scoping Review of Human, Registry, and Preclinical Evidence

Fecal microbiota transplantation (FMT) is being explored as a microbiota-directed intervention for Alzheimer's disease (AD), with evidence drawn mainly from preclinical studies. This scoping review mapped published human reports, registered trials and animal microbiota-transfer studies to inform FMT research in AD. Five human reports, eight unique registered trials and 34 animal studies were included. Four human reports concerned FMT administered for Clostridioides difficile infection (CDI). The remaining report was an uncontrolled five-patient pilot comprising two patients with AD, two with mild cognitive impairment (MCI) and one with frontotemporal dementia (FTD). It described maintained cognition in AD and FTD and improvement or maintenance in MCI. The published human studies were nonrandomized. Among the eight registered trials, two required AD biomarker confirmation and two specified donor-referenced engraftment outcomes. Among 30 animal studies assessing cognition, 24 reported positive findings and six mixed findings. Restriction to genetic/transgenic AD models reduced the positive proportion from 24/30 (80.0%) to 17/23 (73.9%). Cognition-specific randomization and blinding were reported in 16/30 (53.3%) and 4/30 (13.3%) studies, respectively. The evidence supports early-phase investigation, with attention to donor and product characterization, appropriate comparators, and separate measurement of engraftment, microbial function, systemic responses and AD outcomes. Safety data remain insufficient for patients with AD, particularly outside the CDI setting. FMT should remain investigational for AD.