Fecal Microbiota Transplantation and Microbiota‐Based Therapeutics in Allogeneic Hematopoietic Stem Cell Transplantation: Current Evidence and Future Directions

The intestinal microbiome is a key regulator of immune homeostasis, metabolism, and epithelial barrier integrity. In patients with malignant hematological diseases, particularly those undergoing hematopoietic stem cell transplantation, microbiome perturbations by reduced diversity, pathobiont expansion, and loss of beneficial metabolites are common as a consequence of exposure to cytotoxic therapy and broad-spectrum antimicrobials. Accordingly, enteral microbiome manipulation has emerged as a promising strategy. We performed a narrative review of the literature in PubMed/MEDLINE, Embase, and the Web of Science from inception to October 2025. We focused on adult hematology and HSCT populations and synthesized evidence across microbiome-directed interventions, including fecal microbiota transplantation (FMT) and emerging standardized microbiota products, as well as adjunctive strategies such as pre-, pro-, and postbiotics, dietary modulation, and microbiome-sparing antimicrobial practices. Available clinical evidence, predominantly from case series, small cohorts and a limited number of randomized trials, suggests that FMT is feasible in selected immunocompromised patients and may be beneficial for recurrent Clostridioides difficile infection, multidrug-resistant organism decolonization and steroid-refractory gastrointestinal GvHD. Mechanistic data support pleiotropic effects of microbiome restoration, including replenishment of immunoregulatory metabolites, improved colonization resistance and reinforcement of mucosal function. While most reported adverse events are mild, rare transmission events and product variability necessitate for rigorous donor screening, standardized manufacturing and regulatory oversight. Key knowledge gaps include patient selection, optimal timing, dosing strategies, durability of benefit and integration with concurrent medications. In conclusion, microbiome-based interventions may transition from rescue therapy toward a structured component of supportive care in hematologic malignancy management.