Reviews & Analysis

Gastrointestinal motor disorders affect a large proportion of the population worldwide. In this Consensus Statement, the authors describe recommended tests for the investigation of gastric, small bowel and colonic motility, with an emphasis on how best to classify gastrointestinal motor disorders to guide treatment decisions.

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.

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.

Elastography is the most accurate noninvasive approach to assess liver fibrosis in patients with NAFLD. Here, the authors discuss the benefits and limitations of various elastographic modalities, their role in the optimal management of NAFLD and directions for future research.

The stomach responds to injury via two main patterns, the superficial response and the glandular response. In this Review, Sáenz and Mills discuss cellular plasticity and reprogramming in the stomach in the context of disease (such as gastric cancer) and during repair and homeostasis.

If gastrointestinal cancer diagnosis is to be both timely and affordable in the future, the roles of health-care professionals need to be reframed. In this Perspectives, the authors consider how the relationship between medical specialists and generalists can be better integrated for optimal clinical outcomes and patient experience.

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.

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.

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.

Increased relative abundance of Fusobacterium species contributes to the difference in intestinal bacterial composition between healthy individuals and patients with colorectal cancer (CRC). A new study now reveals that live Fusobacterium originating from primary CRC associate with liver metastasis, suggesting a potentially important function for this bacterial genus in metastatic tumour growth.

A growing body of evidence suggests that chronic hepatitis C infection is associated with an increased rate of extrahepatic cancers. In this Review, the authors summarize epidemiological studies exploring this relationship and provide insights into the potential mechanisms underlying a causal link.

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.

Predicting clinical outcomes in cancer using neoantigen burden is imperfect because current algorithms use only the binding affinity of putative neoantigens to HLA. A new study models pancreatic tumour response through a deeper understanding of tumour immunology, providing new tools for identifying neoantigens and characteristics that define their quality.

A growing body of evidence implicates non-coding RNAs (ncRNAs) in liver carcinogenesis. In this Review, the authors summarize the pathological roles of ncRNAs in hepatocellular carcinoma and explore the potential applications of ncRNAs as diagnostic tools and therapeutic targets.

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.

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.

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.

Hirschsprung disease is a serious and potentially fatal condition affecting the enteric nervous system and defined by the absence of enteric neurons in the distal bowel. This Review provides an update on the basic science discoveries that link to clinical manifestations of the disease.