Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.

Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Prophylactic application of a haemostatic gel to the resection field may be an easy way to prevent delayed bleeding, a frequent complication after endoscopic mucosal resection (EMR).

Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown.

RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA therapies have made significant progress in the treatment of genetic liver diseases, exemplified by small interfering RNA treatments for hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation to improve efficacy and safety. RNA-based gene-editing technologies, such as base editor and prime editor clustered regularly interspaced short palindromic repeats systems, also show promise with their ability to minimise genomic rearrangements and cancer risk. While RNA therapies offer high precision, challenges remain in optimising delivery methods and ensuring long-term safety and efficacy. Lipid nanoparticle-mRNA therapeutics, particularly for protein replacement in rare diseases, have gained support from preclinical successes. Compared with viral gene therapies, mRNA therapies present a safer profile with reduced risks of genomic integration and oncogene activation. However, clinical trials, especially for rare diseases, face limitations such as small sample sizes and short observation periods. Further preclinical studies, including non-human primates, will be essential for refining trial designs. Despite their potential, the high costs of RNA therapies pose a challenge that will require cost-utility models to guide pricing and accessibility. Here, we discuss the fundamental aspects of RNA-based therapeutics and showcase the most relevant preclinical and clinical developments in genetic liver metabolic diseases.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC.

Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.

Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals.

The link between gut microbiome and eating behaviours, especially palatable food intake, is a growing focus of scientific investigation. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function and neurobehavioural signalling. This review explores the role of neuroinflammation in dysregulations of food-induced reward signalling and the potential causal role of the gut microbiota on these proinflammatory processes. Particular attention is given to eating disorders (ED, specifically anorexia nervosa, binge eating disorder and bulimia nervosa) and potential links with the gut microbiota, food reward alterations and neuroinflammation. Finally, we propose gut microbiota modulation as a promising therapeutic strategy in food reward alterations and ED.

Given the imperative to combat climate change, reducing the healthcare sector's implications on the environment is crucial.

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all intestinal cell types, including immune, epithelial and stromal cells, have been described in these diseases. The study of IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse cell types, limiting insights. Single-cell omic technologies overcome the intrinsic limitations of bulk analysis and reveal the complexity of multicellular tissues at a cell-by-cell resolution. Within healthy and inflamed intestinal tissues, single-cell omics, particularly single-cell RNA sequencing, have contributed to uncovering novel cell types and cell functions linked to disease activity or the development of complications. Collectively, these results help identify therapeutic targets in difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae or inflammation of the pouch. More recently, single-cell omics have gradually been adopted in studies to understand therapeutic responses, identify mechanisms of drug failure and potentially develop predictors with clinical utility. Although these are early days, such studies lay the groundwork for the implementation in clinical practice of new technologies in diagnostics, monitoring and prediction of disease prognosis. With this review, we aim to provide a comprehensive survey of the studies that have applied single-cell omics to the study of UC or CD, and offer our perspective on the main findings these studies contribute. Finally, we discuss the limitations and potential benefits that the integration of single-cell omics into clinical practice and drug development could offer.

Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a 5-year survival rate of 12%. It has two major molecular subtypes: classical and basal, regulated by the master transcription factors (MTFs) GATA6 and ΔNp63, respectively.

The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management.

Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

Fasting-mimicking diet (FMD) boosts the antitumour immune response in patients with colorectal cancer (CRC). The gut microbiota is a key host immunity regulator, affecting physiological homeostasis and disease pathogenesis.

Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs).

Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively. MASLD is associated with multiple comorbidities including type 2 diabetes, hypertension, dyslipidaemia, decreased bone mineral density, obstructive sleep apnoea, anxiety and depression. Currently, there are no pharmacological treatments available for children, highlighting the urgent need for paediatric clinical trials. A diet low in free sugars is promising for reducing steatosis and decreasing alanine aminotransferase, a surrogate marker for hepatic inflammation. Emerging data indicate that steatosis can be present in children under 6 years of age, which was previously considered rare. The intricate interplay of genetics may inform future therapeutics and prognostication, with the PNPLA3 gene showing the most evidence for association with the risk and severity of steatotic liver disease and steatohepatitis. MASLD is a complex disease affecting one in ten children and is associated with increased early mortality risk. More dedicated studies are needed in children to advance our understanding of this disease and find effective treatments.

Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy.