Reviews & Analysis

Mechanical forces are important for normal gastrointestinal development and function. Now, He et al. have discovered a population of Drosophila midgut epithelial enteroendocrine cell (EEC) precursors that express the mechanosensitive ion channel Piezo, which generates a calcium influx that drives EEC differentiation and proliferation in response to physiological mechanical stimuli.

Exome sequencing of patients with Crohn’s disease (CD) of Ashkenazi Jewish descent and genotyping of large case–control cohorts has identified new CD risk and protective variants of LRRK2, the most common genetic determinant of Parkinson disease. These findings provide new insights into the pathophysiology of these two seemingly unrelated disorders.

In a prospective study of adults with Crohn’s disease or ulcerative colitis, Gracie and colleagues have found evidence for the bi-directional relationship between inflammatory bowel disease (IBD) activity and symptoms of psychological disorders. This study represents an important milestone in our understanding of how the brain and gut interact in IBD.

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.

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.

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.

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.

At the squamocolumnar junction of mice and humans,a new study has identified a unique population of transitional basal cells that express molecular markers of both oesophageal stratified squamous epithelium and gastrointestinal columnar epithelium. These transitional basal cells are an attractive candidate for the cell of origin for Barrett oesophagus.

Oncolytic viruses have made headlines owing to increasing numbers of reports of clinical success. Compelling data now indicate that small anticancer molecules can serve as potent sensitizers of tumour cells in hepatocellular carcinoma to enhance the oncolytic potential of systemically applied viruses.

Although Helicobacter pylori is associated with gastric cancer, bacterial communities that reside in the stomach are mostly unacknowledged. A new study shows that some gastric bacterial communities have emigrated from our mouth, prefer certain neighbours and prefer certain environments. By understanding the interactions of these bacteria, we hope to understand the environment most conducive to gastric cancer carcinogenesis.

Ileocaecal resection has traditionally been reserved for the treatment of biologic-refractory inflammatory, fibrostenotic or fistulizing Crohn's disease of the terminal ileum. Now, for the first time, this surgical approach has been investigated as an initial treatment for steroid or immunomodulator-refractory Crohn's ileitis, in comparison with anti-TNF therapy.

Childhood malnutrition is a global health issue influenced by poorly understood microbial interactions. A new model of co-infection in mice now sheds light on the complex interplay between pathogens, the host and the resident gut microbiota during malnutrition.

The presence of lymph node metastases (LNM) is considered one of the most important features of colorectal cancer (CRC) staging, indicating the need for additional surgery after local excision and adjuvant chemotherapy after surgery. Now, a new study challenges the role of LNM in the progression of CRC.

Non-anatomical resection of colorectal liver metastases is the current preferred approach to maximize sparing of the hepatic parenchyma. A new study raises the question of whether resection in patients with KRAS-mutated colorectal liver metastases should be performed along segmental, anatomical lines to reduce the risk of local liver recurrence.

Various mechanisms eliciting symptoms in GERD and its most common phenotypic presentation, nonerosive reflux disease (NERD), have been suspected and investigated. One study now suggests that superficial nerves in the oesophageal epithelium might have a key role in the pathogenesis of NERD and could represent a potential target for topical therapies.

KRAS oncogene mutations are commonly encountered in pancreatic ductal adenocarcinoma, driving tumour initiation, proliferation, progression and metastasis. Human exosomes engineered to deliver small interfering RNA silencing KRAS^G12D are highly efficient at specifically targeting pancreatic cancer cells to dramatically reduce RAS activation, cancer cell proliferation and metastatic processes.

A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC.

In a new report, adolescents with genotype 2 or 3 HCV infection who were given sofosbuvir and ribavirin showed a near 100% sustained virologic response. This study is the beginning of a new wave of treatments for paediatric HCV infection, forming part of a global strategy to eradicate viral hepatitis.

A new study reveals an involvement of SLC22A3 in the development of familial oesophageal squamous cell carcinoma (ESCC). Reduced expression of SLC22A3 is detected not only in ESCC tumours but also in non-tumour tissues of patients with familial ESCC. Interestingly, adenosine-to-inosine editing of SLC22A3 mRNA is proposed to drive early tumour invasion and metastasis, by inhibiting SLC22A3 expression.

Biosimilar monoclonal antibodies are now being accepted in clinical practice by IBD specialists. However, switching patients already undergoing originator biologic treatment to biosimilars has been debated due to lack of controlled studies. The NOR-SWITCH study now provides novel clinical evidence in switching from originator to biosimilar in patients with IBD.