Reviews & Analysis

The stability of the neuronal circuits and cells of the enteric nervous system can no longer be taken for granted; new evidence suggests astounding rates of apoptosis and neurogenesis.

The intestinal lymphatic vasculature has a range of functions, from maintenance of interstitial fluid balance to transport of antigens, cells, dietary lipids and fat-soluble vitamins. In this Review, Petrova and Bernier-Latmani provide an in-depth overview of intestinal lymphatics, including their roles in human diseases.

Extracellular vesicles have emerged as having key roles in liver disease. In this Review, Szabo and Momen-Heravi discuss the functions of extracellular vesicles in liver disease pathogenesis and progression, and explore their potential use as biomarkers, therapeutic targets and tools for therapy delivery.

NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016.

Imaging and endoscopy remains key to the diagnosis of gastrointestinal malignancies, especially for early disease detection. Here, the authors describe multimodal imaging techniques and how they can be applied along the gastrointestinal tract, in particular for the identification of pre-malignant lesions in the oesophagus, stomach and colon.

A new study shows that the prebiotic inulin improves vascular function in an animal model of cardiovascular disease. A key mechanism for how dietary gut microbiota modulation regulates host physiology through the activities of host–microbiota co-metabolic signalling via bile acids and glucagon-like peptide 1 is also explained.

A new study identifies heterozygous loss-of-function mutations in three additional genes (ALG8, SEC61B and PKHD1) as causative for the development and progression of isolated polycystic liver diseases. Mutations in these genes, together with previously described mutations in other genes (PRKCSH, SEC63, LRP5 and GANAB), might now explain ∼50% of PLD cases.

The clinical management of refractory eosinophilic oesophagitis (EoE) is challenging, owing to the limited data available to guide decision-making. In this Review, Dellon discusses the clinical definition of refractory EoE, examines the causes and predictors of non-response, and highlights both current and emerging treatment modalities for non-responders.

There have been no major improvements in the prevention or treatment of necrotizing enterocolitis (NEC) over the past several decades, and therefore a 'magic bullet' is urgently needed. However, new data demonstrate that disialyllacto-N-tetraose levels in breast milk can predict the risk of NEC, and these findings might provide a strategy for successful intervention.

Acute gastroenteritis precipitates post-infectious IBS in 10–30% of patients. In this Perspectives, Ghoshal and Gwee discuss evidence of overlap between post-infectious IBS, tropical sprue (which can also develop after acute gastroenteritis) and small intestinal bowel overgrowth, and argue that greater understanding of the links between these conditions will improve understanding of IBS pathogenesis.

Gastric cancer is a deadly malignancy and accumulating evidence suggests that epigenetic abnormalities promote carcinogenesis. Here, the authors summarize the gastric cancer epigenome, highlighting key advances from studies of DNA methylation and histone modifications, and how these findings might lead to therapeutic opportunities.

Serotonin is a key intercellular signalling molecule with well-known functions in the gastrointestinal tract, particularly for motility. This Review explores the non-conventional roles of gut-derived serotonin in the gut and other peripheral tissues, including during gastrointestinal inflammation, haematopoiesis, metabolic homeostasis and bone remodelling.

Activation of hepatic stellate cells (HSCs) in liver injury is the primary driver of hepatic fibrosis. In this Review, Tsuchida and Friedman detail the varied intracellular and extracellular signalling pathways leading to HSC activation, as well as the role of HSCs in liver fibrosis resolution and as therapeutic targets.

International guidelines recognize surgery as a standard treatment option for type 2 diabetes mellitus, including in mildly obese individuals who fail to respond to conventional therapies. A new report from the STAMPEDE trial now provides further evidence and emphasizes the need for health care regulators to introduce appropriate reimbursement policies for metabolic surgery.

Lipid droplets (LDs) are dynamic organelles and many metabolic disorders results in abnormal lipid accumulation in the liver. This Review provides insights into LD biology and lipid homeostasis in the liver, as well as the role of LDs in liver diseases, including NAFLD, NASH and hepatitis C.

Cell culture infection models help to develop antiviral agents, but animal models are required to understand complex virus–host interactions and the development of immune therapies. Although identification of the HBV uptake receptor enabled establishing cell lines that replicate HBV from its natural transcription template, animal models supporting the full HBV life cycle are still lacking.

Gastrointestinal malignancies are among the most common human cancers. Genomic and transcriptomic analyses have identified recurring molecular subtypes that suggest important biological differences. Here, the authors review the common themes of gastrointestinal cancer subtypes, as well as how they could be implemented into clinical practice.

Currently, no pharmacological therapies are approved for the treatment of NASH. A new study now identifies CASP8 and FADD-like apoptosis regulator (CFLAR) as a novel suppressor of NASH and its associated disorders in a process dependent on the activation of apoptosis signal-regulating kinase 1 (ASK1).

Gut microbiota research has rapidly evolved, but has yet to translate fully to the clinic. In this Perspectives, Eamonn Quigley explores whether the gut microbiota could be used as a clinical tool in gastrointestinal disease, providing a note of caution to the hype.