Nature Reviews Gastroenterology &Hepatology最新文献

Microbiomes provide key contributions to health and potentially important therapeutic targets. Conceived nearly 30 years ago, the prebiotic concept posits that targeted modulation of host microbial communities through the provision of selectively utilized growth substrates provides an effective approach to improving health. Although the basic tenets of this concept remain the same, it is timely to address certain challenges pertaining to prebiotics, including establishing that prebiotic-induced microbiota modulation causes the health outcome, determining which members within a complex microbial community directly utilize specific substrates in vivo and when those microbial effects sufficiently satisfy selectivity requirements, and clarification of the scientific principles on which the term ‘prebiotic’ is predicated to inspire proper use. In this Expert Recommendation, we provide a framework for the classification of compounds as prebiotics. We discuss ecological principles by which substrates modulate microbiomes and methodologies useful for characterizing such changes. We then propose statistical approaches that can be used to establish causal links between selective effects on the microbiome and health effects on the host, which can help address existing challenges. We use this information to provide the minimum criteria needed to classify compounds as prebiotics. Furthermore, communications to consumers and regulatory approaches to prebiotics worldwide are discussed.

Diet and nutritional metabolites exhibit wide-ranging effects on health and disease partly by altering tissue composition and function. With rapidly rising rates of obesity, there is particular interest in how obesogenic diets influence tissue homeostasis and risk of tumorigenesis; epidemiologically, these diets have a positive correlation with various cancers, including colorectal cancer. The gastrointestinal tract is a highly specialized, continuously renewing tissue with a fundamental role in nutrient uptake and is, in turn, influenced by diet composition and host metabolic state. Intestinal stem cells are found at the base of the intestinal crypt and can generate all mature lineages that comprise the intestinal epithelium and are uniquely influenced by host diet, metabolic by-products and energy dynamics. Similarly, tumour growth and metabolism can also be shaped by nutrient availability and host diet. In this Review, we discuss how different diets and metabolic changes influence intestinal stem cells in homeostatic and pathological conditions, as well as tumorigenesis. We also discuss how dietary changes and composition affect the intestinal epithelium and its surrounding microenvironment.

Tuft cells have gained substantial attention over the past 10 years due to numerous reports linking them with type 2 immunity and microorganism-sensing capacity in many mucosal tissues. This heightened interest is fuelled by their unique ability to produce an array of biological effector molecules, including IL-25, allergy-related eicosanoids, and the neurotransmitter acetylcholine, enabling downstream responses in diverse cell types. Operating through G protein-coupled receptor-mediated signalling pathways reminiscent of type II taste cells in oral taste buds, tuft cells emerge as chemosensory sentinels that integrate luminal conditions, eliciting appropriate responses in immune, epithelial and neuronal populations. How tuft cells promote tissue alterations and adaptation to the variety of stimuli at mucosal surfaces has been explored in multiple studies in the past few years. Since the initial recognition of the role of tuft cells, the discovery of diverse tuft cell effector functions and associated feedback loops have also revealed the complexity of tuft cell biology. Although earlier work largely focused on extraintestinal tissues, novel genetic tools and recent mechanistic studies on intestinal tuft cells established fundamental concepts of tuft cell activation and functions. This Review is an overview of intestinal tuft cells, providing insights into their development, signalling and interaction modules in immunity and other states.