To date, the development of nanomaterials for drug delivery applications has focused on the optimisation of drug-loading capacity, ease of functionalisation, and stimuli-responsive drug release properties. Recent studies have analysed the bio-nano interactions between these nanomaterials and biological fluids, unveiling mechanisms that are critical for the design of 'smart' nano-therapeutics including cellular trafficking dynamics and protein corona formation. However, even though our bodies are covered in ecological communities of symbiotic bacteria -inside and out -there is a paucity of knowledge on how nanomaterials behave when exposed to these microorganisms. Several hundred grams of live bacteria reside in the GI tract at any one time and suppositories and tablets cannot avoid exposure to these bacteria. Similarly, transdermal patches are placed in direct contact with the skin microbiota. These microbial communities have only recently been characterised in terms of their diversity, function, and role in health and disease. Moreover, the human microbiome plays a vital role in human health; it is implicated in many biological processes: harvesting energy, strengthening tissue integrity, protecting against pathogens, regulating host immunity, and vitamin biosynthesis. Gut bacteria metabolise and bioaccumulate drugs before host absorption, in turn affecting drug absorption, efficacy, and side-effect profile. This has profound consequences on the success of pharmaceutical treatments. In this work, we focus on lipidic nanomaterials and examine the effects that humanassociated bacterial species have on their self-assembly and drug release properties. Non-lamellar lipid mesophases are promising drug delivery systems with complex nanostructures that determine the kinetics of drug release. Hydrophilic drugs can be loaded into the internal aqueous channels; hydrophobic drugs in the hydrophobic domains; and amphiphilic drugs at the interface between these domains (Figure ). The marked differences between these domains are key determinants of drug transport, thus ultimately affecting the release rate. The liquid crystalline inverse cubic (V₂) or inverse hexagonal (H₂) nanostructures can be dispersed into solution in the presence of a stabiliser to create cubosomes or hexosomes respectively. Their unique combination of biocompatibility, stability to dilution, dynamic self-assembled structure, and sustained drug release qualities make lipid mesophases an attractive drug delivery vehicle. The nanostructure of the lipid mesophase is determined by the shape and packing behaviour of the constituent lipids. The self-organisation of these lipid assemblies is a dynamic process that is influenced by the surrounding environment. Environmental conditions such as pH, temperature, and level of hydration can influence lipid geometry and packing behaviour, thereby affecting the liquid crystalline nanostructure. This sensitivity to the local environment has been manipulated for biosensing applications and stimuli-responsive drug delivery. While this ability can be exploited for 'smart' drug delivery, it could be responsible for unforeseen changes in drug release properties when the lipidic nanomaterials interact with the human microbiome.