Probiotic therapeutics: A critical review of mechanisms, clinical efficacy, and the frontier of precision microbiome modulation

Probiotic therapeutics are evolving from generalized wellness supplements to precision Live Biotherapeutic Products aimed at specific disease targets.

• The mechanistic framework of probiotic action includes ecological niche modulation, reinforcement of the epithelial barrier, and systemic signaling via the gut-brain axis.
• Clinical efficacy has been established for conditions like antibiotic-associated diarrhea, but outcomes for complex disorders such as irritable bowel syndrome and metabolic syndrome show high variability.
• This variability may be due to critical factors like strain-specificity, host-specific colonization resistance, and a lack of standardized core outcome sets in study design.
• The field is advancing toward precision microbiome modulation with next-generation biotics, synbiotics, and engineered microbial therapeutics.
• Integrating multi-omics technologies with artificial intelligence could be essential for transitioning to personalized, evidence-based clinical practice.

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