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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.
Although metagenomic sequencing has provided unprecedented characterization of the gut microbiome, it gives only indirect evidence of the genes and pathways that might be active. Now, investigators have combined longitudinal sampling with metatranscriptomics and metagenomics in IBD to provide a high-resolution picture of the microbiome's functional dynamics.
RNA interference (RNAi) is a novel concept to target transcripts derived from HBV covalently closed circular DNA. The study by Wooddell et al. investigates the RNAi-based therapy ARC-520 in patients and chimpanzees with chronic HBV infection and uncovers HBV DNA integration as a crucial source of hepatitis B surface antigen, which has not been considered in current strategies to accomplish HBV cure.
The human gut microbiota undergoes dramatic development early in life. Here, the authors explore how this development is influenced by priority effects, whereby the order and timing of microbial species arrival affect community assembly. In turn, factors affecting order and timing, including delivery mode, diet and parenting behaviours, are also discussed.
Neutrophil extracellular traps (NETs) have an important role during infection but they are also related to the exacerbation of inflammation and the development of autoimmunity, cancer metastasis and inappropriate thrombosis. Here, the authors focus on the role of NETs in the liver and gastrointestinal system, outlining their protective and pathological effects and their potential for therapeutic intervention.
Immune checkpoint inhibitors are a novel approach to cancer immunotherapy. However, they are associated with substantial risk of immune-related adverse events, including gastrointestinal toxicity. This Review explores the manifestations of gastrointestinal toxicity with immune checkpoint inhibitor use and insights into its management.
Approximately half of patients diagnosed with oesophageal cancer have metastatic or unresectable disease. Here, the authors discuss the multidisciplinary interventions available to manage dysphagia, improve quality of life and prolong survival in these individuals.