The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.

This Review is an overview of the unique characteristics of cyclodextrin in forming an inclusion complex via host–guest noncovalent interactions. The modification of cyclodextrin advances its application as a pharmaceutical solubilizer, fabrication of functional molecular machines such as polyrotaxane, polypseudorotaxane, and polycatenanes and grafting of cyclodextrin with different linear, branched chain polymers. The different stimuli‐based supramolecular assemblies involving cyclodextrin as a key mediator with linked triggering responses on payload release is highlighted. In addition, the applications of cyclodextrin in diagnostic imaging and medical devices is briefly demonstrated. Cyclodextrin is a relatively low cost, biocompatible, biodegradable, and highly explored material with low toxicity for drug formulation, drug delivery, and wide varieties of other biomedical applications such as those in medical devices fabrication, biosensor, tissue engineering, and bio‐imaging. The toxicological profile of cyclodextrin is well established and safe for human consumption in food and medicine.

Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for the highly efficient in vivo delivery of exogenous mRNA, particularly for COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral lipids, cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent the advances and insights for the design of LNPs, as well as their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as ionizable lipids are the most critical drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines is discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy is explained. Finally, expert opinion on LNPs for mRNA vaccines is discussed, which may address future challenges in developing mRNA vaccines using highly efficient LNPs based on a novel set of ionizable lipids. Developing highly efficient mRNA delivery systems for vaccines with improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.