Table 4.

Comparison of microbial EV therapy vs. live biotherapeutics (LBP) and human cell EV (exosome) therapies.

	Microbial EVs	Live biotherapeutics (LBP)	Human cell EVs (Exosomes)
Pharmacology (PK/PD)	• Multimodal mechanism of action (MoA) • Nanosized EVs enter systemic circulation • Independent of viability • Targeting of specific organs & cellular organelles • Targeting of distant organs (esp. brain) • Efficacious oral application possible	• No penetration of host cells • Generally restricted to the GI tract • Dependent on viability • Targeting of specific organs unfeasible	• Targeting of distant organs unfeasible • Oral administration unfeasible
Safety	• No proliferation • Minimal safety concerns (commensal derived) • Low potential for epigenetic modification	• Uncontrollable proliferation • Concerns for immune-compromised individuals	• Potential for epigenetic modification
CMC	• Minimal storage & stability issues • High yield • Low cost	• Storage & stability hurdles	• Low yield • High cost

PK pharmacokinetic, PD pharmacodynamic, CMC chemistry, manufacturing, and control.