The existing literature exploring the interaction of lipidic materials and bacteria is focussed on antimicrobial applications. and more recently, the fusion dynamics with gram-positive and -negative bacteria. Their work has demonstrated that the cell envelope structure governs the kinetics of lipidic nanocarrier fusion with the cell. Most cubosomes employed for drug delivery are composed of monoolein (MO), a monoacylglycerol that can be hydrolysed by enzymatic digestion to create oleic acid (OA) and glycerol. Thorn et al. have demonstrated ex vivo that a bacterial lipase extracted from an opportunistic human pathogen Pseudomonas cepacia accelerated the digestion of MO cubosomes, thereby 'triggering' release of the entrapped hydrophobic drug cargo. However, live bacteria can express a number of different lipasesfor example, Malassezia globosa secretes 13 different types. Further, different species from the same genus secrete lipases with varying amino acid sequences; the activity of each lipase is dramatically influenced by pH, temperature, and metal ions. As such, little is known about the effects of live bacteria in the native microbiome on lipidic drug delivery systems. In this paper, the behaviour of MO cubic and hexagonal phases when exposed to live bacteria is examined for the first time with regards to the mechanism and kinetics of these effects, and the consequent effect on drug release properties. We have chosen representative bacterial strains of four species that are present within commonly targeted routes of administration to achieve this: Staphylococcus aureus (skin/nasal mucosal membranes), Pseudomonas aeruginosa (pathogenic), Escherichia coli (caecum/colon), Lactobacillus rhamnosus (colon).