Microbial secondary metabolites not only have key roles in microbial processes and relationships but are also valued in various sectors of today’s economy, especially in human health and agriculture. The advent of genome sequencing has revealed a previously untapped reservoir of biosynthetic capacity for secondary metabolites indicating that there are new biochemistries, roles and applications of these molecules to be discovered. New predictive tools for biosynthetic gene clusters (BGCs) and their associated pathways have provided insights into this new diversity. Advanced molecular and synthetic biology tools and workflows including cell-based and cell-free expression facilitate the study of previously uncharacterized BGCs, accelerating the discovery of new metabolites and broadening our understanding of biosynthetic enzymology and the regulation of BGCs. These are complemented by new developments in metabolite detection and identification technologies, all of which are important for unlocking new chemistries that are encoded by BGCs. This renaissance of secondary metabolite research and development is catalysing toolbox development to power the bioeconomy.
Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus–host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed.
Research over the past two decades has established a remarkable ability of the gut microbiota to modulate brain activity and behaviour. Conversely, signals from the brain can influence the composition and function of the gut microbiota. This bidirectional communication across the gut microbiota–brain axis, involving multiple biochemical and cellular mediators, is recognized as a major brain–body network that integrates cues from the environment and the body’s internal state. Central to this network is the gut sensory system, formed by intimate connections between chemosensory epithelial cells and sensory nerve fibres, that conveys interoceptive signals to the central nervous system. In this Review, we provide a broad overview of the pathways that connect the gut and the brain, and explore the complex dialogue between microorganisms and neurons at this emerging intestinal neuroepithelial interface. We highlight relevant microbial factors, endocrine cells and neural mechanisms that govern gut microbiota–brain interactions and their implications for gastrointestinal and neuropsychiatric health.
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