Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.

Here, we evaluate the contribution of AT-rich interaction domain-containing protein 1A (ARID1A), the most frequently mutated member of the SWItch/sucrose non-fermentable (SWI/SNF) complex, in pancreatic homeostasis and pancreatic ductal adenocarcinoma (PDAC) pathogenesis using mouse models.

To determine if human colonic neuromuscular functions decline with increasing age.

Our life expectancy is increasing, leading to a rise in the ageing population. Ageing is associated with a decline in physiological function and adaptive capacity. Altered GI physiology can affect the amount and types of nutrients digested and absorbed as well as impact the intestinal microbiota. The intestinal microbiota is considered a key player in our health, and a variety of studies have reported that microbiota composition is changing during ageing. Since ageing is associated with a decline in GI function and adaptive capacity, it is crucial to obtain insights into this decline and how this is related to the intestinal microbiota in the elderly. Hence, in this review we focus on age-related changes in GI physiology and function, changes of the intestinal microbiota with ageing and frailty, how these are associated and how intestinal microbiota-targeted interventions may counteract these changes.

Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.

With the growing number of novel therapeutic approaches for liver diseases, significant research efforts have been devoted to the development of liquid biopsy tools for precision medicine. This can be defined as non-invasive reliable biomarkers that can supplement and eventually replace the invasive liver biopsy for diagnosis, disease stratification and monitoring of response to therapeutic interventions. Similarly, detection of liver cancer at an earlier stage of the disease, potentially susceptible to curative resection, can be critical to improve patient survival. Circulating extracellular vesicles, nucleic acids (DNA and RNA) and tumour cells have emerged as attractive liquid biopsy candidates because they fulfil many of the key characteristics of an ideal biomarker. In this review, we summarise the currently available information regarding these promising and potential transformative tools, as well as the issues still needed to be addressed for adopting various liquid biopsy approaches into clinical practice. These studies may pave the way to the development of a new generation of reliable, mechanism-based disease biomarkers.

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.

Human gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as Blastocystis, an enteric stramenopiles with worldwide distribution. Here, we surveyed the prevalence and subtype variation of Blastocystis in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between Blastocystis subtypes and identified microbiota-host covariates and quantified microbiota differentiation relative to subtype abundances.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed death-1 (PD-1)/ligand are increasingly used to treat several types of cancer. These drugs enhance antitumour T-cell activity and therefore induce immune-related adverse effects (irAE), of which gastrointestinal (GI) irAE are among the most frequent and severe. This systematic literature review summarises the clinical manifestations, management and pathophysiology of GI irAE due to immune checkpoint inhibitors. GI irAE induced by anti-CTLA-4 are frequent, potentially severe and resemble IBD, whereas those induced by PD-1 blockade seem to be less frequent and clinically more diverse. Baseline symbiotic gut microbiota is associated with an enhanced antitumour response to immune checkpoint inhibitors and an increased susceptibility to developing enterocolitis, in patients treated with anti-CTLA-4. These findings open new perspectives for possible manipulation of the gut microbiota in order to better identify responders to immune checkpoint inhibitors and to increase their efficacy and safety.

Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier.

Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.