HUMAN MICROBIOME AND LIVE BIOTHERAPEUTIC PRODUCTS: REGULATORY ADVANCES AND CLINICAL APPLICATIONS

The human microbiome, comprising trillions of microorganisms residing primarily in the gastrointestinal tract, plays a fundamental role in host metabolism, immunity, and disease pathogenesis. Dysbiosis—an imbalance in microbial community structure and function—has been associated with a wide range of conditions, including Clostridioides difficile infection, inflammatory bowel disease, metabolic disorders, and even oncologic and neurologic diseases. Live biotherapeutic products, defined as biological products containing live microorganisms intended for prevention, treatment, or cure of a disease, represent a novel therapeutic class distinct from conventional probiotics. This review examines the evolving regulatory landscape for live biotherapeutic products, focusing on frameworks developed by the US Food and Drug Administration and the European Medicines Agency, and discusses key clinical applications and evidence through 2023. The most advanced live biotherapeutic products are those targeting recurrent Clostridioides difficile infection, with several candidates demonstrating efficacy in reducing recurrence. Other areas, including ulcerative colitis, atopic dermatitis, and immuno-oncology, are being explored, although evidence is less mature. Critical challenges include manufacturing standardization, strain characterization, engraftment and colonization dynamics, safety in immunocompromised populations, and the need for well-designed clinical trials. Future directions include defined consortia, engineered microbes, and microbiome-based diagnostics for patient stratification. Overall, live biotherapeutic products hold significant promise, but rigorous regulatory and scientific standards are essential to translate microbiome science into clinical benefit.