Host-diet-microbiota interplay in intestinal nutrition and health

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction. Quantitative or qualitative alterations in intestinal resident microbe composition can lead to microbiota imbalance, namely intestinal dysbiosis, in both flies and humans. Intestinal microbiota dysbiosis, in turn, deregulates host physiology and contributes to the development, as well as the severity, of various types of intestinal and other diseases, including inflammatory diseases of the gut, diabetes, neurodegenerative diseases, and cancer. image