Pharmacomicrobiomics-driven targeted drug delivery for precision microbiome modulation

The human microbiome can actively influence how drugs are handled and processed in our body. More knowledge of host-microbiome-drug interactions has shifted drug delivery from current approaches to precision therapeutics.

The review is to evaluate various targeted strategies and mechanisms of drug delivery systems (DDS) driven by pharmacomicrobiomics. Moreover, the pharmacomicrobiomics-based DDS will also be discussed in terms of their therapeutic applications, translation, and new technologies for microbiome precision.

Assessment on the latest development on microbiome-drug interactions and microbiome-based drug delivery strategies, including microbial enzyme activated prodrugs, nano- and micro-particle systems, probiotics, prebiotics, postbiotics, bacteriophages, genetically modified microorganisms, smart materials, and niche-selective delivery systems. The researchers also investigated clinical evidence, security, regulatory issues, Pharmacoeconomics and new emerging multi-omics and AI based strategies.

Microbiome-targeted DDS enable localized drug activation, site-specific delivery, and reduced systemic exposure. Enzyme-responsive systems achieved up to a 3-fold increase in local drug concentration, while SER-109 (VOWST) reduced CDI recurrence to 12% versus 40% with placebo at 8 weeks. FMT combined with pembrolizumab achieved objective responses in 40% (6/15) of previously non-responsive melanoma patients. Engineered microbial therapeutics, including SYNB1618 and AG013, further demonstrate the growing translational potential of programmable microbiome-based therapies.

Pharmacymicrobiomics-driven drug delivery systems (DDS) represent an innovative approach to precision therapeutics utilizing microbes. However, challenges such as individual microbiome variability, unvalidated biomarkers, safety concerns, intricate regulatory hurdles, and inconsistent translational outcomes from preclinical studies persist. A comprehensive integration of omics data and interdisciplinary collaboration is essential to enhance the predictability of microbiome therapies. Future efforts should focus on microbiome profiling, validating mechanism-based biomarkers, scalable manufacturing, and conducting clinical studies to define patient selection, ensure therapeutic consistency, and confirm long-term benefits.