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"The daisies of the gut" — Cover image supplied by Maxime M. Mahe and Holly M. Poling, Department of Pediatric Surgery at Cincinnati Children's Hospital Medical Center, USA. Human intestinal organoids (HIOs) were generated from pluripotent stem cells through a directed differentiation process in vitro. The HIOs were then transplanted under the kidney capsule of immunocompromised mice, where they developed into complex intestinal tissue resembling the human intestine. The image depicts an epithelial cross-section of a transplanted HIO. Epithelial cells form saccular structures at the base of the epithelium called crypts, which are surrounded by endothelial vessels.
2017 has witnessed key advances in knowledge about the metabolic capacities of the gut microbiota, enabling the progression of our understanding of the principles driving xenobiotic–bacteria–host interplay. This research paves the way for the long road towards personalized medicine and nutrition, which could be based on gut microbial metabolism.
In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies.
The central studies published in 2017 address novel IBD therapeutic strategies and prediction of the future disease course or response to a distinct therapy. Together, these studies contribute to the understanding of the regulation of mucosal homeostasis and at the same time serve to develop novel personalized treatment algorithms in patients in whom a severe disease course can be predicted.
In 2017, the FDA approved regorafenib and nivolumab for the treatment of patients with hepatocellular carcinoma following prior sorafenib treatment, opening the door for an effective systemic second-line therapy in advanced disease. By contrast, the addition of sorafenib to transarterial chemoembolization with drug-eluting beads did not improve progression-free survival in the intermediate disease stage.
High stromal cellularity in pancreatic cancer is an important factor for ineffective treatment and molecular studies. In 2017, major advancements were made in transcriptional characterization, treatment delivery and clinical regimes, raising hope for a breakthrough against this deadly disease.
2017 has witnessed major advances in gut stem cell and cancer stem cell research, delivering key insights into their regulation, more defined culture methods and novel stem cell markers that collectively drive us ever closer to breakthroughs for regenerative medicine and cancer treatment in the clinic.
Cellular senescence is induced in response to various stresses and can either prevent or fuel disease and tumorigenesis. Here, the authors provide an overview of senescence aimed at gastroenterologists and hepatologists and detail how modulation of senescence might be used for therapeutic purposes.
Hepatitis E virus (HEV) is a public health concern in both developing and developed countries. Here, the authors describe advances in understanding HEV biology, clinical infection and the challenges still to be overcome in HEV research, particularly with respect to cell culture and animal models.
Bile acids link the gut microbiota to both hepatic and intestinal metabolism, and this tripartite relationship has been implicated in gastrointestinal disease. In this Review, the authors outline the mechanistic links between bile acid–microbiota crosstalk and gastrointestinal inflammation and carcinogenesis, with a specific emphasis on the major bile-acid-sensing receptors.