Reviews & Analysis

The enteric nervous system is vital for life, and its dysfunction participates not only in digestive disorders, but also in diseases of the central nervous system (CNS). Here, Rao and Gershon discuss the gastrointestinal consequences of neurological disorders, the acquisition of CNS disease in the gut and the spread of pathology along the gut–brain axis.

Since the recognition of reflux oesophagitis as a disease entity, scientists and clinicians have commonly assumed that the first step in its pathogenesis was a loss of superficial epithelial cells, brought about by caustic acid injury. However, new data suggests that it is time to reconsider this concept.

Symptom-based diagnostic criteria have been criticized for being overly complex and performing modestly in differentiating organic from functional gastrointestinal diseases. The new Rome IV criteria now supersede Rome III. In general, these minor amendments are unlikely to lead to substantial improvement in accuracy and use in routine clinical care. Is a different approach required in future?

This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

Gastrointestinal dysfunction is very common in patients with systemic sclerosis, and often severely reduces quality of life. In this Review, Emmanuel discusses optimal strategies to identify and manage gastrointestinal complications in patients with systemic sclerosis, and outlines potential new therapies.

The global burden of malnutrition (undernutrition, micronutrient deficiencies or obesity) is considerable and associated with risk of excess mortality and long-term adverse outcomes. Concerted action to achieve agreed global nutrition targets is proposed for the next decade, which must be coupled with the political will to address the root causes of malnutrition and implement evidence-based strategies.

Obesity is a risk factor for several noncommunicable diseases, but some individuals with obesity remain metabolically healthy throughout life; whether these individuals are at risk of developing NAFLD is uncertain. In a new study, Chang et al. showed a statistically significant, graded relationship between BMI and NAFLD in metabolically healthy individuals.

Most colorectal polyps can now be resected endoscopically using either mucosal resection or submucosal dissection. Although the former is an established technique, the latter has seen slow adoption in the West. In this Review, the authors summarize the indications for both procedures and discuss new advances in endoscopic polyp surgery.

Liver regeneration is important in both the context of homeostasis and in recovery from disease or injury. In this Review, Forbes and Newsome describe the mechanisms underlying liver regeneration and the experimental models used to study this process, as well as discussing how liver regeneration is clinically relevant.

Elucidating the entire complexity of biological functions in the liver is vital to understand its key role in the progression of complex diseases. A new mouse study integrates complementary '–omics' data across various environmental states using the liver as a platform for multiomics analysis and identifies new mechanisms in hepatic mitochondrial function.

Faecal microbiota transplantation (FMT) has emerged as a successful treatment forClostridium difficileinfection (CDI). Here, the authors describe the latest information on the mechanisms of action of FMT in the context of CDI and how it might restore the gut microbial community and structure. They also explore future applications of FMT beyond CDI.

Elastography techniques for the noninvasive assessment of liver fibrosis, disease severity and prognosis are increasingly included in guidelines and clinical practice. In this Review, the authors summarize the problems of noninvasive tests in general, and provide an overview on available techniques and developments in liver elastography.

This Review discusses the mechanisms via which changes in the gut can influence the development and progression of NAFLD. Understanding of such mechanisms is hoped to pave the way for new treatments for what has become the most common form of liver disease.

A new study reports that activation of neutrophils leads to the release of neutrophil extracellular traps (NETs) and coagulation, which then promote development of a tumorigenic microenvironment in the small intestine. These findings provide novel insights into the role of neutrophils in cancer and suggest enticing directions for future research.

A recent study reports on drug clearance in newborn babies after in utero exposure to anti-TNF antibodies, infliximab and adalimumab. As women with IBD are increasingly exposed to these drugs due to changing treatment paradigms and earlier diagnosis, this commentary explores these clinically important results.

In a recent study, Kawada et al. conducted a retrospective analysis of paediatric patients who had undergone lower gastrointestinal endoscopy to evaluate its use as a diagnostic tool. This under-studied area deserves critique within a modern framework of expectation for the routine yield for this invasive investigation in standard paediatric gastroenterology practice.

Subclassification of colorectal cancers can inform patient prognosis and response to treatment. Beyond these functions, a recent study demonstrates that molecular subtyping can also play an important part in rational drug discovery, uncovering new indications for drugs previously thought ineffective.

Upper gastrointestinal tract function is regulated by vagovagal neurocircuits, comprising brainstem nuclei that integrate visceral sensory information and provide vagal motor output. Here, Travagli and Anselmi describe the organization of these neurocircuits and their plasticity in response to stressors. The influence of gastrointestinal peptides on vagovagal neurons is also discussed.

Research has highlighted the importance of the stroma in pancreatic cancer, in particular the role of complex interactions between cancer and stromal cells. A new study describes a novel mechanism by which stromal pathways can be modulated to inhibit tumour growth. The findings support the concept that a multipronged therapeutic approach targeting pancreatic cancer cells and cancer stroma could improve clinical outcomes for this disease.

Altered patterns of gut microbiota maturation are associated with impaired growth and undernutrition in early childhood. A closer look at historical contingency and the ecological processes that determine microbial community assembly might enlighten strategies to restore a health-promoting gut ecosystem.